DOCSLIB.ORG

Chapter 14 Essential Questions • Before This Class, Ask Your Self the Following Questions: – How Fast an Enzyme Could Accelerate a Reaction? Reginald H

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Chapter 14 Essential Questions • Before This Class, Ask Your Self the Following Questions: – How Fast an Enzyme Could Accelerate a Reaction? Reginald H Hanjia’s Biochemistry Lecture Hanjia’s Biochemistry Lecture Chapter 14 Essential Questions • Before this class, ask your self the following questions: – How fast an enzyme could accelerate a reaction? Reginald H. Garrett Charles M. Grisham – Why enzyme could accelerate a reaction? Mechanisms of Enzyme Action – How enzymes could accelerate a reaction? – What are the universal chemical principles that Դৣ influence the mechanisms of enzymes and allow us to ᑣ٫݅ ፐำᆛઠ understand their enormous catalyyptic power? http://lms.ls.ntou.edu.tw/course/106 hji@[email protected] dtdu.tw 2 Hanjia’s Biochemistry Lecture Hanjia’s Biochemistry Lecture Outline How Much Enzyme-Induced Rate Accelerations? • Part I: The general concepts of enzyme catalysis • TillTypically 107 – 1014 greater – What are the magnitudes of enzyme-induced rate accelerations? • Why? 2 reasons…. – What role does transition-state stabilization play in enzyme – Sta biliza tion o f tititttransition state catalysis? – Destabilization of ES – How does destabilization of ES affect enzyme catalysis? • due to strain, desolvation or electrostatic effects – How tightly do transition-state analogs bind to the active site? • How? 5 catalytic mechanisms…. • Part II: The mechanisms of catalysis – covalent catalysis • Part III: What can be learned from typical enzyme – general acid or base catalysis mechanisms? – Low-Barrier H-bonds – 3 examples: serine protease, aspartic protease and chorismate – metal ion catalysis mutase! – ppyroximity/orientation ( Near-Attack Conformation). 3 4 Hanjia’s Biochemistry Lecture Hanjia’s Biochemistry Lecture 14. 1 What Are the Magnitudes of Enzyme- What is transition state? Induced Rate Accelerations? • The structure represents, as nearly as possible, the transition between the reactants and products, and it is known as the transition state. • Transition =\= intermediates ( Ex: ES or EP) – Intermediates are longer-lived, with lifetimes in the range of 10-13 sec to 10-3 sec. – A typical transition state has very short lifetime, typically 10-13 sec. - - H-O-H + Cl- H-O H Cl HO- + H-Cl Transition state existed even there is no enzyme 5 6 Hanjia’s Biochemistry Lecture Hanjia’s Biochemistry Lecture Reason 1: Transition-State Stabilization Reason 2: Destabilize ES complex • With enzyme, the transition state changed from X‡ to The dissociation constant for the EX‡ enzyme –substrate complex ‡ Ks • Activation energy difference (G ) between ES and ES E+S ‡ ‡ EX is smaller than between S and X , therefore the [E] [S] Ks = catalyypzed rate of product formation will be faster. [ES] No enzyme! Enzyme catalysis The dissociation constant for the transition-state complex K EX‡ T E+X‡ [E] [X‡] ‡ ‡ Gu >Ge KT = [EX‡] Enzyme catalysis requires To stabilize EX‡ more! KT< Ks b Dissociation of ES facilitates reaction ke/ku KS/KT 7 8 Hanjia’s Biochemistry Lecture Hanjia’s Biochemistry Lecture The binding of S to E must be favorable Destabilization of ES but not too favorable! • ES cannot be "too tight" – The idea is to make Strain the energy barrier between ES and EX‡ small! • Intrinsic binding energy Gb • Some amino acid of enzyme favor to bind substrate, making Desolvation Gb negative! • Compensation • Entropy loss due to the binding of E and S (T S) • Destabilization of ES ( Gd) by strain, distortion, desolvation , Distortion and similar effects. 9 Hanjia’s Biochemistry Lecture Hanjia’s Biochemistry Lecture No Destabilization of ES No Catalysis • Net energy difference • RiiRaising the energy o fESif ES raises the ra t!te! between E + S and the ES complex is the sum of …. 1. intrinsic binding energy, Gb 2. the entropy loss on binding, -TS 3. the dis tor tion energy, . Gd 12 Hanjia’s Biochemistry Lecture Hanjia’s Biochemistry Lecture 14.4 How Tiggyhtly Do Transition-State First TSA case: Proline racemase Analogs Bind to the Active Site? • ThTo have b bttetter k/kke/kuvalKlue, K /K shldbbi!hould be big! • Proline racemase, a bacterial enzyme, catalyzes S T the interconversion of D and L-proline. –KT should be small – The affinity of the enzyme for the transition state may • The TSA, pyrrole-2-carboxylate, bound to the be 10 -20 to 10-26 M! enzyme 160 times more tightly than L-proline • Can we prove such kind of?f tight binding? • Transition state analogs (TSAs) – are stable molecules that are chemically and structurally similar to the transition state – bind more strongly than a substrate – transition-state analogs are ppyotent enzyme inhibitors 13 14 Hanjia’s Biochemistry Lecture Hanjia’s Biochemistry Lecture TSAs are also very strong inhibitors (b) Pu rin e ri boside inhi bi ts aden osin e deamin ase. Th e Figure 14. 6 (a ) Phosp hog lyco lo hy droxamate is an ana log o f t he hydrated form is an analog of the transition state of the enediolate transition state of the yeast aldolase reaction. 15 reaction. 16 Hanjia’s Biochemistry Lecture Hanjia’s Biochemistry Lecture Transition-State Analogs Make Our World EndofPart1End of Part 1 Better • Enzymes are often targets for drugs and • Ask yourself… other beneficial agents – What is transition state? • Transition state analogs often make ideal – What is intermediate? enzyme inhibitors – What is the two reasons that enzyme could – Enalapril and Aliskiren lower blood pressure accelerate reaction? – Statins lower serum cholesterol – Wha t e ffec ts cou ld des ta bilize ES comp lex ? – Protease inhibitors are AIDS drugs – What is TSA? What can TSA tell us? – Juvenile hormone esterase is a pesticide target – Tamiflu is a viral neuraminidase inhibitor 17 18 Hanjia’s Biochemistry Lecture Hanjia’s Biochemistry Lecture 14. 5 What Are the Mechanisms of Catalysis? Protein Motions Are Essential to Enzyme Catalysis • Protein motions are essential to enzyme • Proteins are constantly moving catalysis – bonds vibrate, side chains bend and rotate, backbone loops wiggle and sway, and whole domains move as a • 5 major mechanisms: unit – Enzymes facilitate formation of near-attack • Protein motions support catalysis in several ways. complexes Active site conformation changes can: – Covalent catalysis – Assist substrate binding – General acid-base catalysis – Bring catalytic groups into position – Low-barrier hydrogen bonds – IdInduce f ormati on of fNAC NACs – Assist in bond making and bond breaking – Metal ion catalysis – Fac ilita te convers ion o f su bs tra te to pro duc t 19 20 Hanjia’s Biochemistry Lecture Hanjia’s Biochemistry Lecture Example: Human cyclophilin A Evident of enzyme movement NMR showed that several active-site residues undergo a prollilylisomerase, whic h greater motion during catalysis than residues elsewhere catalyzes the interconversion in the protein. btbetween trans and cis conformations of proline in peptides. 21 22 Hanjia’s Biochemistry Lecture Hanjia’s Biochemistry Lecture Some Review of General Chemistry How to read and write mechanisms Step 1 • The custom of writing chemical reaction by Gilbert Newton Lewis and Sir Robert • In written mechanisms, a curved arrow shows RbiRobinson the movement of an electron pair • Review of the concepts • And thus the movement of a pair of electrons – Lewis dot structures from a filled orbital to an empty one – Valence electrons and formal charge • A fllfull arrow hea d representtltis an electron pair – Formal charge = group number – nonbonding •A half arrowhead represents a single electron eltlectrons – (1/2 s hare d e lec trons ) – Electronegativity is also important: – F > O > N > C > H 23 24 Hanjia’s Biochemistry Lecture Hanjia’s Biochemistry Lecture How to read and write mechanisms How to read and write mechanisms Step 2 Step 3 For a bdbond-bkibreaking event, the arrow beg ins in the m iddle o f • It has been es timat ed tha t 75% o f the s teps in the bond, and the arrow points to the atom that will accept the enzyme reaction mechanisms are proton (H+) electrons. tftransfers. • If the proton is donated or accepted by a group on the enzyme, it is often convenient (and traditional) to represent the group as “B”, for For a bond-making event, the arrow begins at the source of “base”, even if B is protonated and behaving as the electrons (for example, a nonbonded pair), and the arrowhead points to the atom where the new bond will be an acid: formed. 25 26 Hanjia’s Biochemistry Lecture Hanjia’s Biochemistry Lecture How to read and write mechanisms How to read and write mechanisms Step 4 • It is important to appreciate that a proton transfer can change a nucleophile into an electrophile, and vice versa. • Thus, it is necessary to consider: – The protonation states of substrate and active-site residues An active-site histidine, which might normally be protonated, can – How pKa values can change in the be deprotonated by another group environment of the active site and then act as a base, accepting a proton from the substrate. 27 28 Hanjia’s Biochemistry Lecture Hanjia’s Biochemistry Lecture How to read and write mechanisms Mechanism 1: Near-attack complexes Water can often act as an acid or base at the active site • X-ray crystal structure studies have shown that the through proton transfer with an assisting active-site residue: reacting atoms and catalytic groups are precisely positioned for their roles. • The preorganization – selects substrate conformations – the reacting atoms are in van der Waals contact – at an ang le resem bling the bon dtd to be forme did in the transition state • Thomas Bruice has termed such arrangements This type of chemistry is the basis for general acid-base near-attack conformations (NACs) catalyy(sis (discussed on p pgages 430-431). • NACs are precursors to reaction transition states 29 30 Hanjia’s Biochemistry Lecture Hanjia’s Biochemistry Lecture Enzymes facilitate formation of near- Requirements of the formation of near- attack complexes attack complexes Figure 14.7 NACs are • In the absence of an enzyme, potential characterized as having reactant molecules adopt a NAC only reacting atoms within 3.2 Å and an approach angle of Ʋ15Ʊ about 0.
Load more

Recommended publications
  • Yeast Genome Gazetteer P35-65
    gazetteer Metabolism 35 tRNA modification mitochondrial transport amino-acid metabolism other tRNA-transcription activities vesicular transport (Golgi network, etc.) nitrogen and sulphur metabolism mRNA synthesis peroxisomal transport nucleotide metabolism mRNA processing (splicing) vacuolar transport phosphate metabolism mRNA processing (5’-end, 3’-end processing extracellular transport carbohydrate metabolism and mRNA degradation) cellular import lipid, fatty-acid and sterol metabolism other mRNA-transcription activities other intracellular-transport activities biosynthesis of vitamins, cofactors and RNA transport prosthetic groups other transcription activities Cellular organization and biogenesis 54 ionic homeostasis organization and biogenesis of cell wall and Protein synthesis 48 plasma membrane Energy 40 ribosomal proteins organization and biogenesis of glycolysis translation (initiation,elongation and cytoskeleton gluconeogenesis termination) organization and biogenesis of endoplasmic pentose-phosphate pathway translational control reticulum and Golgi tricarboxylic-acid pathway tRNA synthetases organization and biogenesis of chromosome respiration other protein-synthesis activities structure fermentation mitochondrial organization and biogenesis metabolism of energy reserves (glycogen Protein destination 49 peroxisomal organization and biogenesis and trehalose) protein folding and stabilization endosomal organization and biogenesis other energy-generation activities protein targeting, sorting and translocation vacuolar and lysosomal
    [Show full text]
  • Exploring the Chemistry and Evolution of the Isomerases
    Exploring the chemistry and evolution of the isomerases Sergio Martínez Cuestaa, Syed Asad Rahmana, and Janet M. Thorntona,1 aEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, United Kingdom Edited by Gregory A. Petsko, Weill Cornell Medical College, New York, NY, and approved January 12, 2016 (received for review May 14, 2015) Isomerization reactions are fundamental in biology, and isomers identifier serves as a bridge between biochemical data and ge- usually differ in their biological role and pharmacological effects. nomic sequences allowing the assignment of enzymatic activity to In this study, we have cataloged the isomerization reactions known genes and proteins in the functional annotation of genomes. to occur in biology using a combination of manual and computa- Isomerases represent one of the six EC classes and are subdivided tional approaches. This method provides a robust basis for compar- into six subclasses, 17 sub-subclasses, and 245 EC numbers cor- A ison and clustering of the reactions into classes. Comparing our responding to around 300 biochemical reactions (Fig. 1 ). results with the Enzyme Commission (EC) classification, the standard Although the catalytic mechanisms of isomerases have already approach to represent enzyme function on the basis of the overall been partially investigated (3, 12, 13), with the flood of new data, an integrated overview of the chemistry of isomerization in bi- chemistry of the catalyzed reaction, expands our understanding of ology is timely. This study combines manual examination of the the biochemistry of isomerization. The grouping of reactions in- chemistry and structures of isomerases with recent developments volving stereoisomerism is straightforward with two distinct types cis-trans in the automatic search and comparison of reactions.
    [Show full text]
  • (10) Patent No.: US 8119385 B2
    US008119385B2 (12) United States Patent (10) Patent No.: US 8,119,385 B2 Mathur et al. (45) Date of Patent: Feb. 21, 2012 (54) NUCLEICACIDS AND PROTEINS AND (52) U.S. Cl. ........................................ 435/212:530/350 METHODS FOR MAKING AND USING THEMI (58) Field of Classification Search ........................ None (75) Inventors: Eric J. Mathur, San Diego, CA (US); See application file for complete search history. Cathy Chang, San Diego, CA (US) (56) References Cited (73) Assignee: BP Corporation North America Inc., Houston, TX (US) OTHER PUBLICATIONS c Mount, Bioinformatics, Cold Spring Harbor Press, Cold Spring Har (*) Notice: Subject to any disclaimer, the term of this bor New York, 2001, pp. 382-393.* patent is extended or adjusted under 35 Spencer et al., “Whole-Genome Sequence Variation among Multiple U.S.C. 154(b) by 689 days. Isolates of Pseudomonas aeruginosa” J. Bacteriol. (2003) 185: 1316 1325. (21) Appl. No.: 11/817,403 Database Sequence GenBank Accession No. BZ569932 Dec. 17. 1-1. 2002. (22) PCT Fled: Mar. 3, 2006 Omiecinski et al., “Epoxide Hydrolase-Polymorphism and role in (86). PCT No.: PCT/US2OO6/OOT642 toxicology” Toxicol. Lett. (2000) 1.12: 365-370. S371 (c)(1), * cited by examiner (2), (4) Date: May 7, 2008 Primary Examiner — James Martinell (87) PCT Pub. No.: WO2006/096527 (74) Attorney, Agent, or Firm — Kalim S. Fuzail PCT Pub. Date: Sep. 14, 2006 (57) ABSTRACT (65) Prior Publication Data The invention provides polypeptides, including enzymes, structural proteins and binding proteins, polynucleotides US 201O/OO11456A1 Jan. 14, 2010 encoding these polypeptides, and methods of making and using these polynucleotides and polypeptides.
    [Show full text]
  • Amino Acid Residue. Chorismate Mutase by Variation of a Single
    Modulation of the allosteric equilibrium of yeast chorismate mutase by variation of a single amino acid residue. R Graf, Y Dubaquié and G H Braus J. Bacteriol. 1995, 177(6):1645. Downloaded from Updated information and services can be found at: http://jb.asm.org/content/177/6/1645 These include: CONTENT ALERTS Receive: RSS Feeds, eTOCs, free email alerts (when new articles cite this article), more» http://jb.asm.org/ on March 22, 2013 by guest Information about commercial reprint orders: http://journals.asm.org/site/misc/reprints.xhtml To subscribe to to another ASM Journal go to: http://journals.asm.org/site/subscriptions/ JOURNAL OF BACTERIOLOGY, Mar. 1995, p. 1645–1648 Vol. 177, No. 6 0021-9193/95/$04.0010 Copyright q 1995, American Society for Microbiology Modulation of the Allosteric Equilibrium of Yeast Chorismate Mutase by Variation of a Single Amino Acid Residue RONEY GRAF,† YVES DUBAQUIE´,‡ AND GERHARD H. BRAUS* Institut fu¨r Mikrobiologie, Biochemie & Genetik, Friedrich-Alexander Universita¨t Erlangen-Nu¨rnberg, D-91058 Erlangen, Germany Received 26 September 1994/Accepted 11 January 1995 Chorismate mutase (EC 5.4.99.5) from the yeast Saccharomyces cerevisiae is an allosteric enzyme which can be locked in its active R (relaxed) state by a single threonine-to-isoleucine exchange at position 226. Seven new replacements of residue 226 reveal that this position is able to direct the enzyme’s allosteric equilibrium, without interfering with the catalytic constant or the affinity for the activator. Downloaded from Chorismate is the last common precursor of the amino acids amino acid 226 of yeast chorismate mutase to glycine and tyrosine, phenylalanine, and tryptophan and an important in- alanine (small), aspartate and arginine (charged), serine (hy- termediate in the biosynthesis of other aromatic compounds in drophilic, similar to the wild-type threonine), cysteine (sulfur fungi, bacteria, and plants (9).
    [Show full text]
  • O O2 Enzymes Available from Sigma Enzymes Available from Sigma
    COO 2.7.1.15 Ribokinase OXIDOREDUCTASES CONH2 COO 2.7.1.16 Ribulokinase 1.1.1.1 Alcohol dehydrogenase BLOOD GROUP + O O + O O 1.1.1.3 Homoserine dehydrogenase HYALURONIC ACID DERMATAN ALGINATES O-ANTIGENS STARCH GLYCOGEN CH COO N COO 2.7.1.17 Xylulokinase P GLYCOPROTEINS SUBSTANCES 2 OH N + COO 1.1.1.8 Glycerol-3-phosphate dehydrogenase Ribose -O - P - O - P - O- Adenosine(P) Ribose - O - P - O - P - O -Adenosine NICOTINATE 2.7.1.19 Phosphoribulokinase GANGLIOSIDES PEPTIDO- CH OH CH OH N 1 + COO 1.1.1.9 D-Xylulose reductase 2 2 NH .2.1 2.7.1.24 Dephospho-CoA kinase O CHITIN CHONDROITIN PECTIN INULIN CELLULOSE O O NH O O O O Ribose- P 2.4 N N RP 1.1.1.10 l-Xylulose reductase MUCINS GLYCAN 6.3.5.1 2.7.7.18 2.7.1.25 Adenylylsulfate kinase CH2OH HO Indoleacetate Indoxyl + 1.1.1.14 l-Iditol dehydrogenase L O O O Desamino-NAD Nicotinate- Quinolinate- A 2.7.1.28 Triokinase O O 1.1.1.132 HO (Auxin) NAD(P) 6.3.1.5 2.4.2.19 1.1.1.19 Glucuronate reductase CHOH - 2.4.1.68 CH3 OH OH OH nucleotide 2.7.1.30 Glycerol kinase Y - COO nucleotide 2.7.1.31 Glycerate kinase 1.1.1.21 Aldehyde reductase AcNH CHOH COO 6.3.2.7-10 2.4.1.69 O 1.2.3.7 2.4.2.19 R OPPT OH OH + 1.1.1.22 UDPglucose dehydrogenase 2.4.99.7 HO O OPPU HO 2.7.1.32 Choline kinase S CH2OH 6.3.2.13 OH OPPU CH HO CH2CH(NH3)COO HO CH CH NH HO CH2CH2NHCOCH3 CH O CH CH NHCOCH COO 1.1.1.23 Histidinol dehydrogenase OPC 2.4.1.17 3 2.4.1.29 CH CHO 2 2 2 3 2 2 3 O 2.7.1.33 Pantothenate kinase CH3CH NHAC OH OH OH LACTOSE 2 COO 1.1.1.25 Shikimate dehydrogenase A HO HO OPPG CH OH 2.7.1.34 Pantetheine kinase UDP- TDP-Rhamnose 2 NH NH NH NH N M 2.7.1.36 Mevalonate kinase 1.1.1.27 Lactate dehydrogenase HO COO- GDP- 2.4.1.21 O NH NH 4.1.1.28 2.3.1.5 2.1.1.4 1.1.1.29 Glycerate dehydrogenase C UDP-N-Ac-Muramate Iduronate OH 2.4.1.1 2.4.1.11 HO 5-Hydroxy- 5-Hydroxytryptamine N-Acetyl-serotonin N-Acetyl-5-O-methyl-serotonin Quinolinate 2.7.1.39 Homoserine kinase Mannuronate CH3 etc.
    [Show full text]
  • Syntheses of Chorismate Analogs for Investigation of Structural Requirements for Chorismate Mutase
    Syntheses of Chorismate Analogs for Investigation of Structural Requirements for Chorismate Mutase by Chang-Chung Cheng B.S., Department of Chemistry National Chung-Hsing University 1986 Submitted to the Department of Chemistry in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in Organic Chemistry at the Massachusetts Institute of Technology May, 1994 © 1994 Chang-Chung Cheng All rights reserved The author hereby grants to MIT permission to reproduce and to distribute publicly paper and electronic copies of this thesis document in whole or in oart. Signature of Author... ............ ............ ......................................................... Department of Chemistry May 18, 1994 Certified by...................................... Glenn A. Berchtold Thesis Supervisor Accepted by..........................................-. ,..... ......................................................... Glenn A. Berchtold Science Chairman, Departmental Committee on Graduate Studies JUN 2 1 1994 LjENrVUVk*_ This doctoral thesis has been examined by a Committee of the Department of Chemistry as Follows: Professor Frederick D. Greene, II......... .......... Chairman Professor Glenn A. Berchtold .ThS................................ Thesis Supervisor Professor Julius Rebek, Jr............... .. ............................................L% 1 Foreword Chang-Chung (Cliff) Cheng's Ph. D. thesis is a special thesis for me because of our association with the individual who supervised his undergraduate research and since Cliff will be the last student to receive the Ph. D. from me during my career at M.I.T.. Cliff received the B.S. degree in Chemistry from National Chung-Hsing University, Taichung, Taiwan in June 1986, and he enrolled in our doctoral program in September 1989. During his undergraduate career Cliff was engaged in research under the supervision of Professor Teng-Kuei Yang. Professor Yang also received his undergraduate training in chemistry at National Chung-Hsing University before coming to the United States to complete the Ph.
    [Show full text]
  • Building Microbial Factories for The
    Contents lists available at ScienceDirect Metabolic Engineering journal homepage: www.elsevier.com/locate/meteng Building microbial factories for the production of aromatic amino acid pathway derivatives: From commodity chemicals to plant-sourced natural products ∗ Mingfeng Caoa,b,1, Meirong Gaoa,b,1, Miguel Suásteguia,b, Yanzhen Meie, Zengyi Shaoa,b,c,d, a Department of Chemical and Biological Engineering, Iowa State University, USA b NSF Engineering Research Center for Biorenewable Chemicals (CBiRC), Iowa State University, USA c Interdepartmental Microbiology Program, Iowa State University, USA d The Ames Laboratory, USA e School of Life Sciences, No.1 Wenyuan Road, Nanjing Normal University, Qixia District, Nanjing, 210023, China ARTICLE INFO ABSTRACT Keywords: The aromatic amino acid biosynthesis pathway, together with its downstream branches, represents one of the Aromatic amino acid biosynthesis most commercially valuable biosynthetic pathways, producing a diverse range of complex molecules with many Shikimate pathway useful bioactive properties. Aromatic compounds are crucial components for major commercial segments, from De novo biosynthesis polymers to foods, nutraceuticals, and pharmaceuticals, and the demand for such products has been projected to Microbial production continue to increase at national and global levels. Compared to direct plant extraction and chemical synthesis, Flavonoids microbial production holds promise not only for much shorter cultivation periods and robustly higher yields, but Stilbenoids Benzylisoquinoline alkaloids also for enabling further derivatization to improve compound efficacy by tailoring new enzymatic steps. This review summarizes the biosynthetic pathways for a large repertoire of commercially valuable products that are derived from the aromatic amino acid biosynthesis pathway, and it highlights both generic strategies and spe- cific solutions to overcome certain unique problems to enhance the productivities of microbial hosts.
    [Show full text]
  • POLSKIE TOWARZYSTWO BIOCHEMICZNE Postępy Biochemii
    POLSKIE TOWARZYSTWO BIOCHEMICZNE Postępy Biochemii http://rcin.org.pl WSKAZÓWKI DLA AUTORÓW Kwartalnik „Postępy Biochemii” publikuje artykuły monograficzne omawiające wąskie tematy, oraz artykuły przeglądowe referujące szersze zagadnienia z biochemii i nauk pokrewnych. Artykuły pierwszego typu winny w sposób syntetyczny omawiać wybrany temat na podstawie możliwie pełnego piśmiennictwa z kilku ostatnich lat, a artykuły drugiego typu na podstawie piśmiennictwa z ostatnich dwu lat. Objętość takich artykułów nie powinna przekraczać 25 stron maszynopisu (nie licząc ilustracji i piśmiennictwa). Kwartalnik publikuje także artykuły typu minireviews, do 10 stron maszynopisu, z dziedziny zainteresowań autora, opracowane na podstawie najnow­ szego piśmiennictwa, wystarczającego dla zilustrowania problemu. Ponadto kwartalnik publikuje krótkie noty, do 5 stron maszynopisu, informujące o nowych, interesujących osiągnięciach biochemii i nauk pokrewnych, oraz noty przybliżające historię badań w zakresie różnych dziedzin biochemii. Przekazanie artykułu do Redakcji jest równoznaczne z oświadczeniem, że nadesłana praca nie była i nie będzie publikowana w innym czasopiśmie, jeżeli zostanie ogłoszona w „Postępach Biochemii”. Autorzy artykułu odpowiadają za prawidłowość i ścisłość podanych informacji. Autorów obowiązuje korekta autorska. Koszty zmian tekstu w korekcie (poza poprawieniem błędów drukarskich) ponoszą autorzy. Artykuły honoruje się według obowiązujących stawek. Autorzy otrzymują bezpłatnie 25 odbitek swego artykułu; zamówienia na dodatkowe odbitki (płatne) należy zgłosić pisemnie odsyłając pracę po korekcie autorskiej. Redakcja prosi autorów o przestrzeganie następujących wskazówek: Forma maszynopisu: maszynopis pracy i wszelkie załączniki należy nadsyłać w dwu egzem­ plarzach. Maszynopis powinien być napisany jednostronnie, z podwójną interlinią, z marginesem ok. 4 cm po lewej i ok. 1 cm po prawej stronie; nie może zawierać więcej niż 60 znaków w jednym wierszu nie więcej niż 30 wierszy na stronie zgodnie z Normą Polską.
    [Show full text]
  • Saccharomyces Cerevisiae—An Interesting Producer of Bioactive Plant Polyphenolic Metabolites
    International Journal of Molecular Sciences Review Saccharomyces Cerevisiae—An Interesting Producer of Bioactive Plant Polyphenolic Metabolites Grzegorz Chrzanowski Department of Biotechnology, Institute of Biology and Biotechnology, University of Rzeszow, 35-310 Rzeszow, Poland; [email protected]; Tel.: +48-17-851-8753 Received: 26 August 2020; Accepted: 29 September 2020; Published: 5 October 2020 Abstract: Secondary phenolic metabolites are defined as valuable natural products synthesized by different organisms that are not essential for growth and development. These compounds play an essential role in plant defense mechanisms and an important role in the pharmaceutical, cosmetics, food, and agricultural industries. Despite the vast chemical diversity of natural compounds, their content in plants is very low, and, as a consequence, this eliminates the possibility of the production of these interesting secondary metabolites from plants. Therefore, microorganisms are widely used as cell factories by industrial biotechnology, in the production of different non-native compounds. Among microorganisms commonly used in biotechnological applications, yeast are a prominent host for the diverse secondary metabolite biosynthetic pathways. Saccharomyces cerevisiae is often regarded as a better host organism for the heterologous production of phenolic compounds, particularly if the expression of different plant genes is necessary. Keywords: heterologous production; shikimic acid pathway; phenolic acids; flavonoids; anthocyanins; stilbenes 1. Introduction Secondary metabolites are defined as valuable natural products synthesized by different organisms that are not essential for growth and development. Plants produce over 200,000 of these compounds, which mostly arise from specialized metabolite pathways. Phenolic compounds play essential roles in interspecific competition and plant defense mechanisms against biotic and abiotic stresses [1] and radiation, and might act as regulatory molecules, pigments, or fragrances [2].
    [Show full text]
  • The Chemistry and Evolution of Enzyme Function
    The Chemistry and Evolution of Enzyme Function: Isomerases as a Case Study Sergio Mart´ınez Cuesta EMBL - European Bioinformatics Institute Gonville and Caius College University of Cambridge A thesis submitted for the degree of Doctor of Philosophy 31st July 2014 This dissertation is the result of my own work and contains nothing which is the outcome of work done in collaboration except where specifically indicated in the text. No part of this dissertation has been submitted or is currently being submitted for any other degree or diploma or other qualification. This thesis does not exceed the specified length limit of 60.000 words as defined by the Biology Degree Committee. This thesis has been typeset in 12pt font using LATEX according to the specifications de- fined by the Board of Graduate Studies and the Biology Degree Committee. Cambridge, 31st July 2014 Sergio Mart´ınezCuesta To my parents and my sister Contents Abstract ix Acknowledgements xi List of Figures xiii List of Tables xv List of Publications xvi 1 Introduction 1 1.1 Chemistry of enzymes . .2 1.1.1 Catalytic sites, mechanisms and cofactors . .3 1.1.2 Enzyme classification . .5 1.2 Evolution of enzyme function . .6 1.3 Similarity between enzymes . .8 1.3.1 Comparing sequences and structures . .8 1.3.2 Comparing genomic context . .9 1.3.3 Comparing biochemical reactions and mechanisms . 10 1.4 Isomerases . 12 1.4.1 Metabolism . 13 1.4.2 Genome . 14 1.4.3 EC classification . 15 1.4.4 Applications . 18 1.5 Structure of the thesis . 20 2 Data Resources and Methods 21 2.1 Introduction .
    [Show full text]
  • A Glutamate Residue in the Catalytic Center of the Yeast Chorismate
    Proc. Natl. Acad. Sci. USA Vol. 94, pp. 8491–8496, August 1997 Biochemistry A glutamate residue in the catalytic center of the yeast chorismate mutase restricts enzyme activity to acidic conditions (Claisen rearrangementysite-directed mutagenesis) GEORG SCHNAPPAUF*, NORBERT STRA¨TER†,WILLIAM N. LIPSCOMB†, AND GERHARD H. BRAUS*‡ *Institut fu¨r Mikrobiologie, Georg-August-Universita¨t,Grisebachstrasse 8, D-37077 Go¨ttingen, Germany; and †Gibbs Chemical Laboratory, Harvard University, 12 Oxford Street, Cambridge, MA 02138 Contributed by William N. Lipscomb, May 27, 1997 ABSTRACT Chorismate mutase acts at the first branch- pseudodiaxial form in dynamic equilibrium with the point of aromatic amino acid biosynthesis and catalyzes the pseudodiequatorial form (11). It is assumed that the reaction conversion of chorismate to prephenate. Comparison of the is accelerated by binding of this active conformer to the x-ray structures of allosteric chorismate mutase from the enzyme, which locks the substrate via a series of electrostatic yeast Saccharomyces cerevisiae with Escherichia coli chorismate and hydrogen bonding and van der Waals interactions in the mutaseyprephenate dehydratase suggested conserved active requisite chair conformation for rearrangement (12–16). Fur- sites between both enzymes. We have replaced all critical thermore, the transition state might be stabilized by electro- amino acid residues, Arg-16, Arg-157, Lys-168, Glu-198, Thr- static interactions with active site residues (10, 17). In an 242, and Glu-246, of yeast chorismate mutase by aliphatic alternative mechanism an acidic residue is proposed to pro- amino acid residues. The resulting enzymes exhibit the neces- tonate the ether oxygen O7 of the substrate chorismate (9).
    [Show full text]
  • All Enzymes in BRENDA™ the Comprehensive Enzyme Information System
    All enzymes in BRENDA™ The Comprehensive Enzyme Information System http://www.brenda-enzymes.org/index.php4?page=information/all_enzymes.php4 1.1.1.1 alcohol dehydrogenase 1.1.1.B1 D-arabitol-phosphate dehydrogenase 1.1.1.2 alcohol dehydrogenase (NADP+) 1.1.1.B3 (S)-specific secondary alcohol dehydrogenase 1.1.1.3 homoserine dehydrogenase 1.1.1.B4 (R)-specific secondary alcohol dehydrogenase 1.1.1.4 (R,R)-butanediol dehydrogenase 1.1.1.5 acetoin dehydrogenase 1.1.1.B5 NADP-retinol dehydrogenase 1.1.1.6 glycerol dehydrogenase 1.1.1.7 propanediol-phosphate dehydrogenase 1.1.1.8 glycerol-3-phosphate dehydrogenase (NAD+) 1.1.1.9 D-xylulose reductase 1.1.1.10 L-xylulose reductase 1.1.1.11 D-arabinitol 4-dehydrogenase 1.1.1.12 L-arabinitol 4-dehydrogenase 1.1.1.13 L-arabinitol 2-dehydrogenase 1.1.1.14 L-iditol 2-dehydrogenase 1.1.1.15 D-iditol 2-dehydrogenase 1.1.1.16 galactitol 2-dehydrogenase 1.1.1.17 mannitol-1-phosphate 5-dehydrogenase 1.1.1.18 inositol 2-dehydrogenase 1.1.1.19 glucuronate reductase 1.1.1.20 glucuronolactone reductase 1.1.1.21 aldehyde reductase 1.1.1.22 UDP-glucose 6-dehydrogenase 1.1.1.23 histidinol dehydrogenase 1.1.1.24 quinate dehydrogenase 1.1.1.25 shikimate dehydrogenase 1.1.1.26 glyoxylate reductase 1.1.1.27 L-lactate dehydrogenase 1.1.1.28 D-lactate dehydrogenase 1.1.1.29 glycerate dehydrogenase 1.1.1.30 3-hydroxybutyrate dehydrogenase 1.1.1.31 3-hydroxyisobutyrate dehydrogenase 1.1.1.32 mevaldate reductase 1.1.1.33 mevaldate reductase (NADPH) 1.1.1.34 hydroxymethylglutaryl-CoA reductase (NADPH) 1.1.1.35 3-hydroxyacyl-CoA
    [Show full text]