DOCSLIB.ORG

The 29Th Annual Symposium of the Protein Society: Program & Abstracts

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The 29Th Annual Symposium of the Protein Society: Program & Abstracts PROGRAM PLANNING COMMITTEE Jim Wells, Ph.D. (Chair) Oscar Millet, Ph.D Mark A. Lemmon, Ph.D. Professor and Chair, Dept of Structural Biology Unit Professor and Chair, Dept of Pharmaceutical Chemistry CIC bioGUNE Biochemistry and Biophysics University of California, San University of Pennsylvania Francisco Perelman School of Medicine Miquel Pons, Ph.D. Gary Pielak, Ph.D. Professor, Dept of Organic Chemistry Distinguished Term Professor of Chemistry, Universitat de Barcelona Biochemistry and Biophysics University of North Carolina, Chapel Hill THANK YOU TABLE OF CONTENTS Symposium Overview .................................................................................................... 3 Executive Council & Leadership ................................................................................. 4 Committees ...................................................................................................................... 5 Protein Society Awards ................................................................................................. 6 Call for 2015 Nominations ............................................................................................... 8 Hotel Floorplan ............................................................................................................... 9 General Information .................................................................................................... 10 Travel Awards ................................................................................................................ 12 Donor Acknowledgements ......................................................................................... 13 Daily Program ............................................................................................................... 14 Day 1 ................................................................................................................................14 Day 2................................................................................................................................ 17 Day 3 ................................................................................................................................21 Day 4............................................................................................................................... 24 Poster Sessions ............................................................................................................. 26 Exhibitors ....................................................................................................................... 47 Exhibitor Workshops .................................................................................................. 54 Speaker Abstracts ......................................................................................................... 55 Poster Abstracts ............................................................................................................ 71 Author Index ............................................................................................................... 274 THANK YOU THE 2014 PROGRAM PLANNING COMMITTEE Todd O. Yeates, Ph.D. Jennifer R. Potts, Ph.D. Professor, Department of Chemistry and Professor and Chair of Molecular Biochemistry Biophysics University of California, Los Angeles Department of Biology The University of York Tarun Kapoor, Ph.D. Pels Family Professor Laboratory of Chemistry and Cell Biology The Rockefeller University CORPORATE SUPPORT The Protein Society is grateful to the following corporate partnerns for supporting the 28th Annual Symposium & The Protein Society: 28TH ANNUAL SYMPOSIUM SPONSORS Proteins in Disease & Therapeutics Research Session Best Poster Competition Complimentary Tote Bags 2014 CORPORATE MEMBERS Gold Level Bronze Level SYMPOSIUM OVERVIEW DAY 1 DAY 2 DAY 3 DAY 4 SUNDAY JULY 27TH MONDAY JULY 28TH TUESDAY JULY 29TH WEDNESDAY JULY 30TH 7:00 AM Members Business Meeting/New Member Welcome Breakfast (75 min) - Marina Room 8:30 AM Opening Plenary Session Protein Proteins in Protein Proteins In Closing Plenary Session & & 2014 Hans Neurath Evolution Disease & Engineering Dynamic & 2014 Stein & Moore Award Winner Talk Grand HAll C Thera- & Synthetic Driven Award Winner Talk Grand Hall C & D peutics Biology Processes Grand Hall C & D Grand HAll D Grand HAll C Grand HAll D 9:40 AM Translation Bacterial Protein Membrane & Folding Interactions Degra- Proteins & Grand HAll C Grand Hall D dation Receptors Grand HAll C Grand HAll D 11:30 AM 11:30 -Exhibits & Poster Displays LUNCH (2 hrs) - Grand Hall A & B (2 hrs) Exhibitor Workshop Exhibitor Workshop Exhibitor Workshop GE Healthcare NanoTemper GE Healthcare EW I-47 NEW Amersham™ 600 Technologies EW III-49 Multimodal Imager series (CCD-based Some like it hot: Determination chromatography: A new camera systems) of Biomolecular Interactions generation of high selectivity (1 hr) - Gaslamp A using MicroScale media for challenging Thermophoresis purifications (1 hr) - Gaslamp A (1 hr) - Gaslamp A All Lunch Workshops from Noon - 1PM Workshop: Undergrad Educator’s Workshop: Workshop: Workshop: How to Research Luncheon How to Write WikiPedia for How to Improve Your Session (1 hr) an Effective Protein Navigate End of Program Writing (1 hr) Bankers Hill Paper Scientists Your Career (1 hr) Bankers Hill (1 hr) (1 hr) (1 hr) Gaslamp C & D Gaslamp C & D Bankers Hill Gaslamp C & D 1:30 PM Frontier Proteins in Chemical Cellular Plenary Awards Session High- Altered Biology & Structures 1:30 PM - 5:50 PM Throughput States Enzymology Grand HAll D Techniques Grand HAll D Grand HAll C Grand Hall C & D Grand HAll C 4:30 PM Exhibits & Poster Displays (2 hrs) - Grand Hall A & B 7:00 PM Networking Dinners (3hrs) Members Reception - Locations Vary (3hrs) - Please View the 8:00 PM Education & Mentoring Program Addendum for Committees’ Mixer Location (3 hrs) Kin Spa Pool Deck, 3rd Floor Following the Symposium, please take a few moments to share your feedback when you receive the Attendee Survey 3 EXECUTIVE COUNCIL & LEADERSHIP President Secretary/Treasurer Past-President James Bowie, University of Jacquelyn Fetrow, University of Lynne Regan, Yale University California, Los Angeles Richmond Lars Baltzer, Uppsala Paula Booth, University Charles Brooks, III, Johannes Buchner, University of Bristol University of Michigan Technische Universität München Zengyi Chang, Peking Stewart Fisher, SL Amy Keating, Jacqui Matthews, University Fisher Consulting Massachusetts Institute University of Sydney of Technology Haruki Nakamura, Andreas Plückthun, Catherine Royer, Michael Summers, Osaka University Universität Zurich Rensselaer Polytechnic University of Maryland, Institute Baltimore County Sarah Teichmann, Brian Matthews (ex officio), Jody McGinness (ex officio), EMBL-EBI/Wellcome Trust Editor in Chief, University of Executive Director, The Protein Sanger Institute Oregon Society 4 NOMINATING COMMITTEE ABSTRACT REVIEW COMMITTEE Mary Munson, University of Massachusetts John Osterhout, Angelo State University (Chair) Medical School (Chair) Cory L Brooks, California State University - Fresno Judith Frydman, Stanford University Christopher Bystroff, Rensselaer Polytechnic Matthais Mann, Max-Planck-Institut für Biochemie Institute Thomas Magliery, The Ohio State University Paola Di Lello, Genentech, Inc. Andrew Miranker, Yale University John J. Dwyer, Ferring Research Institute Mary Munson, University of Massachusetts Francisco J. Enguita, University of Lisbon Medical School Angelo M. Figueiredo, University of East Anglia Brenda Schulman, St. Jude Children's Research Hospital Azucena G. Horta, Universidad Autonoma de Nuevo Leon Wei Yang, LMB, NIDDK, NIH Mary Konkle, Eastern Illinois Univerrsity PUBLICATIONS COMMITTEE Suresh Kumar, University of Arkansas Amy Keating, Massachusetts Institute of Patricia Ann Mabrouk, Northeastern University Technology (Chair) Todd Naumann, USDA-ARS-NCAUR James Bowie, University of California - Los Angeles Matthew Torres, Georgia Institute of Technology Arthur Palmer, III, Columbia University Sudha Veeraraghavan, University of Maryland Lynne Regan, Yale University School of Pharmacy Jacquelyn Fetrow, University of Richmond Bo Zhang, DuPont Industrial Biosciences Zhiwen Zhang, Santa Clara University Brian Matthews, University of Oregon MENTORING COMMITTEE Andrew Vendel, Eli Lilly and Company (Chair) Judith Klein-Seetharaman, University of Pittsburgh Blake Hill, Medical College of Wisconsin School of Medicine Kevin Lumb, Merck & Company Giovanna Ghirlanda, Arizona State University Matthew Cordes, University of Arizona Janel McLean, Vanderbilt University Medical Center Patricia Jennings, University of California, San Diego Carly Huitema, SIAF institute Olve Peersen, Colorado State University Eric Sundberg, University of Maryland School of Medicine Stephen Fuchs, Tufts University EDUCATION COMMITTEE Ellis Bell, University of Richmond (Chair) John Osterhout, Angelo State University Margaret Cheung, University of Houston Jane Richardson, Duke University Matthew Gage, Northern Arizona University Srebrenka Robic, Agnes Scott College Lisa Gentile, University of Richmond Michael Summers, University of Maryland - Peter Kahn, Rutgers University Baltimore County/HHMI Betsy Komives, University of California - San Diego Frieda Texter, Albright College Mary Konkle, Eastern Illinois University Jeff Watson, Gonzaga University 5 2014 PROTEIN SOCIETY AWARDS The Carl Brändén Award, sponsored by Rigaku Corporation, is given to an outstanding protein scientist
Load more

Recommended publications
  • Functional Assignments in the Enolase Superfamily: Investigations of Two Divergent Groups of D-Galacturonate Dehydratases and Galactarate Dehydratase-Iii
    FUNCTIONAL ASSIGNMENTS IN THE ENOLASE SUPERFAMILY: INVESTIGATIONS OF TWO DIVERGENT GROUPS OF D-GALACTURONATE DEHYDRATASES AND GALACTARATE DEHYDRATASE-III BY FIONA PATRICIA GRONINGER-POE i DISSERTATION Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biochemistry in the Graduate College of the University of Illinois at Urbana-Champaign, 2014 Urbana, Illinois Doctoral Committee: Professor John A. Gerlt, Chair Professor John E. Cronan, Jr. Associate Professor Rutilo Fratti Associate Professor Raven H. Huang ABSTRACT More than a decade after the genomic age, full genome sequencing is cost-effective and fast, allowing for the deposit of an ever increasing number of DNA sequences. New fields have arisen from this availability of genomic information, and the way we think about biochemistry and enzymology has been transformed. Unfortunately, there is no robust method for accurately determining the functions of enzymes encoded by these sequences that matches the speed in which genomes are deposited into public databases. Functional assignment of enzymes remains of utmost importance in understanding microbial metabolism and has applications in agriculture by examining bacterial plant pathogen metabolism and additionally in human health by providing metabolic context to the human gut microbiome. To aid in the functional identification of proteins, enzymes can be grouped into superfamilies which share common structural motifs as well as mechanistic features. To this end, the enolase superfamily is an excellent model system for functional assignment because more than half of the members still lack functional identification. Structurally, these enzymes contain substrate specificity residues in the N-terminal capping domain and catalytic residues in the C-terminal barrel domain.
    [Show full text]
  • The Structure of Neurospora Crassa 3-Carboxy-Cis,Cis-Muconate Lactonizing Enzyme, a ␤ Propeller Cycloisomerase
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Structure, Vol. 10, 483–492, April, 2002, 2002 Elsevier Science Ltd. All rights reserved. PII S0969-2126(02)00744-X The Structure of Neurospora crassa 3-Carboxy-cis,cis-Muconate Lactonizing Enzyme, a ␤ Propeller Cycloisomerase Tommi Kajander,1 Michael C. Merckel,1 ing the structural basis for different alternatives for catal- Andrew Thompson,2 Ashley M. Deacon,3 ysis in MLEs could therefore aid in understanding and Paul Mazur,4 John W. Kozarich,4,6 engineering enzymes for degradation of xenobiotic pol- and Adrian Goldman1,5 lutants, such as fluoroaromatics. 1 Institute of Biotechnology MLEs convert cis,cis-muconates to muconolactones Research Program in Structural Biology in soil microbes as part of the ␤-ketoadipate pathway. and Biophysics This aerobic catabolic pathway converts aromatics, such University of Helsinki as the breakdown products of lignin, through catechol FIN-00014 Helsinki and protocatechuate to citric acid cycle intermediates. Finland The two major branches of the ␤-ketoadipate pathway 2 EMBL are the catechol branch, with cis,cis-muconate lactoniz- Grenoble Outstation ing enzymes, and the protocatechuate branch (Figure 38024 Grenoble 1), with carboxy-cis,cis-muconate lactonizing enzymes France (CMLEs). 3 Stanford Synchrotron Radiation Laboratory The evolutionary origins of these enzymes are surpris- Menlo Park, California 94025 ingly divergent, both in terms of sequence similarity and 4 Merck Research Laboratories functional properties (Table 1). Three different classes of Rahway, New Jersey 07065 lactonizing enzymes can be distinguished. The bacterial MLEs contain an unusual TIM barrel [3] and are closely related to mandelate racemase [4].
    [Show full text]
  • Functional and Physiological Discovery in the Mannonate Dehydratase Subgroup of the Enolase Superfamily
    FUNCTIONAL AND PHYSIOLOGICAL DISCOVERY IN THE MANNONATE DEHYDRATASE SUBGROUP OF THE ENOLASE SUPERFAMILY BY DANIEL JOSEPH WICHELECKI DISSERTATION Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biochemistry in the Graduate College of the University of Illinois at Urbana-Champaign, 2014 Urbana, Illinois Doctoral Committee: Professor John Gerlt, Chair Professor John Cronan Professor Scott Silverman Professor Wilfred van der Donk ABSTRACT In the current post-genomic world, the exponential amassing of protein sequences is overwhelming the scientific community’s ability to experimentally assign each protein’s function. The use of automated, homology-based annotations has allowed a reprieve from this efflux of data, but has led to widespread misannotation and nonannotation in protein sequence databases. This dissertation details the functional and physiological characterization of the mannonate dehydratase subgroup (ManD) of the enolase superfamily (ENS). The outcome affirms the dangers of homology-based annotations while discovering novel metabolic pathways. Furthermore, the experimental verification of these pathways ( in vitro and in vivo ) has provided a platform to test the general strategies for improved functional and metabolic characterization being developed by the Enzyme Function Initiative (EFI). Prior to this study, one member of the ManD subgroup had been characterized and was shown to dehydrate D-mannonate to 2-keto-3-deoxy-D-gluconate. Forty-two additional members of the ManD, selected from across the sequence space of the subgroup, were screened for activity and kinetic constants were determined. The members of the once isofunctional subgroup were found to differ in both catalytic efficiency and substrate specificity: 1) high 3 4 -1 -1 efficiency (k cat /K M = 10 to 10 M s ) dehydration of D-mannonate, 2) low efficiency (k cat /K M = 10 1 to 10 2 M-1s-1) dehydration of D-mannonate and/or D-gluconate, and 3) no-activity with either D-mannonate or D-gluconate (or any other acid sugar tested).
    [Show full text]
  • Crystal Structure Analysis of a Bacterial Lysozyme at Very High Resolution
    The crystal structure of a bacterial lysozyme at atomic resolution Dissertation zur Erlangung des akademischen Grades doctor rerum naturalium (Dr. rer. nat.) vorgelegt dem Rat der Chemisch-Geowissenschaftlichen Fakultät der Friedrich-Schiller-Universität Jena von Diplom-Chemikerin Astrid Rau geboren am 01.06.1974 in Saalfeld Gutachter: 1. Prof. Dr. R. Hilgenfeld 2. Prof. Dr. D. Klemm Tag der öffentlichen Verteidigung: 01.06.2005 TABLE OF CONTENTS 1. INTRODUCTION 1 1.1 Milestones in lysozyme research 1 1.2 Definition and classification of lysozymes 5 1.3 Catalytic mechanisms of lysozymes 7 1.4 Chalaropsis-type lysozymes 9 1.5 Cellosyl – a Ch-type lysozyme from Streptomyces coelicolor 12 1.7 Aim of the project 13 2. MATERIALS AND METHODS 14 2.1 Materials 14 2.1.1 Proteins 14 2.1.2 Carbohydrates 14 2.1.3 Chemicals 15 2.1.4 Crystallisation screens 15 2.1.5 Dialysing tools, assays, crystallisation materials and cryo-tools 15 2.1.6 Laboratory equipment and synchrotron facilities 16 2.2 Methods 17 2.2.1 Determination of protein purity 17 2.2.2 Determination of protein concentration 18 2.2.3 Dialysis 18 2.2.4 Sample concentration 18 2.2.5 Crystallisation 18 2.2.6 Heavy atom and polysaccharide soaks 19 2.2.7 Cryocooling 20 2.2.8 Data acquisition and processing 20 2.2.8.1 Native data collection on the monoclinic crystal form 21 2.2.8.2 Native data collection on the hexagonal crystal form 22 2.2.8.3 MAD data collection 22 2.2.8.4 Data collection on heavy-atom derivatised crystals 24 2.2.8.5 Collection and processing of atomic-resolution data 25 I 2.2.9 Phase determination 27 2.2.9.1 Molecular replacement 28 2.2.9.2 Multiple wavelength anomalous dispersion 29 2.2.9.3 Multiple isomorphous replacement with anomalous scattering 29 2.2.10 Model building and electron-density maps 31 2.2.11 Structure refinement 33 2.2.12 Validation of model quality 35 3.
    [Show full text]
  • Representing Structure-Function Relationships in Mechanistically Diverse Enzyme Superfamilies
    Representing Structure-Function Relationships in Mechanistically Diverse Enzyme Superfamilies S.C.-H. Pegg, S. Brown, S. Ojha, C.C. Huang, T.E. Ferrin, and P.C. Babbitt Pacific Symposium on Biocomputing 10:358-369(2005) REPRESENTING STRUCTURE-FUNCTION RELATIONSHIPS IN MECHANISTICALLY DIVERSE ENZYME SUPERFAMILIES SCOTT C.-H. PEGG†, SHOSHANA BROWN†, SUNIL OJHA†, CONRAD C. HUANG*, THOMAS E. FERRIN*†, PATRICIA C. BABBITT†* †Dept. of Biopharmaceutical Sciences and *Dept. of Pharmaceutical Chemistry University of California, San Francisco, 94143 The prediction of protein function from structure or sequence data remains a problem best addressed by leveraging information available from previously determined structure-function relationships. In the case of enzymes, the study of mechanistically diverse superfamilies can provide a rich source of structure-function information useful in functional determination and enzyme engineering. To access these relationships using a computational resource, several issues must be addressed regarding the representation of enzyme function, the organization of structure-function relationships in the superfamily context, the handling of misannotations, and reliability of classifications and evidence. We discuss here our approaches to solving these problems in the development of a Structure-Function Linkage Database (SFLD) (online at http://sfld.rbvi.ucsf.edu). 1. Introduction The solution of a protein’s three-dimensional structure often does not immediately lead to the determination of its function.1 Typically, we
    [Show full text]
  • Tools for Maximizing the Efficiency of Protein
    SEARCH FOR EXTRATERRESTRIAL LIFE USING CHIRAL MOLECULES: MANDELATE RACEMASE AS A TEST CASE A Thesis Presented to The Academic Faculty by Tracey Lyn Thaler In Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the School of Chemistry & Biochemistry Georgia Institute of Technology May 2007 SEARCH FOR EXTRATERRESTRIAL LIFE USING CHIRAL MOLECULES: MANDELATE RACEMASE AS A TEST CASE Approved by: Dr. Andreas S. Bommarius, Advisor Dr. Christoph J. Fahrni School of Chemical & Biomolecular School of Chemistry & Engineering Biochemistry Georgia Institute of Technology Georgia Institute of Technology Dr. Rick P. Trebino Dr. Phillip R. Gibbs School of Physics Chief Science Officer Georgia Institute of Technology Stheno Corporation Dr. Donald F. Doyle School of Chemistry & Biochemistry Georgia Institute of Technology Date Approved: 03-28-07 ACKNOWLEDGEMENTS First and foremost I would like to thank my advisor Andy Bommarius for his support and encouragement over the past six and half years. I am also thankful to my thesis committee members: Donald Doyle, Christoph Fahrni, Phillip Gibbs and Rick Trebino for their patience as well as guidance. I would especially like to the thank Phillip Gibbs, who was not only the mastermind behind my thesis topic, but has always been encouraging in suggesting ideas to enhance my work. I would also like to thank my lab members past and present. Karen Polizzi has been a wonderful friend and colleague. We had many great conversations about α/β-barrel enzymes, which led to enhance my knowledge in this area. James Broering, also a great friend, has been very supportive of my efforts and helpful in teaching me about DSC, also I have found his cynical views refreshing.
    [Show full text]
  • The Structure of a New Crystal Form of Muconate Lactonizing Enzyme Compared with Mandelate Racemase and Enolase
    Proc. Natl. Acad. Sci. USA Vol. 95, pp. 10396–10401, September 1998 Biochemistry Evolution of an enzyme active site: The structure of a new crystal form of muconate lactonizing enzyme compared with mandelate racemase and enolase MIRIAM SARAH HASSON*†,ILME SCHLICHTING*‡,JAVAD MOULAI*, KIRK TAYLOR§,WILLIAM BARRETT§, i GEORGE L. KENYON¶,PATRICIA C. BABBITT¶,JOHN A. GERLT§ ,GREGORY A. PETSKO*,** AND DAGMAR RINGE* *Departments of Biochemistry and Chemistry and the Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02254-9110; †Department of Biological Sciences, Purdue University, West Lafayette, IN 47907-1392; §Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742; ¶Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143-0446; and iDepartment of Biochemistry, University of Illinois, Urbana, IL 61801 Contributed by Gregory A. Petsko, June 25, 1998 ABSTRACT Muconate lactonizing enzyme (MLE), a com- ponent of the b-ketoadipate pathway of Pseudomonas putida,is a member of a family of related enzymes (the ‘‘enolase superfamily’’) that catalyze the abstraction of the a-proton of a carboxylic acid in the context of different overall reactions. New untwinned crystal forms of MLE were obtained, one of which diffracts to better than 2.0-Å resolution. The packing of the octameric enzyme in this crystal form is unusual, because the asymmetric unit contains three subunits. The structure of MLE presented here contains no bound metal ion, but is very similar to a recently determined Mn21-bound structure. Thus, absence of the metal ion does not perturb the structure of the active site. The structures of enolase, mandelate racemase, and MLE were superimposed.
    [Show full text]
  • The Enzyme Function Initiative John A
    Current Topic pubs.acs.org/biochemistry The Enzyme Function Initiative John A. Gerlt,*, ,! Karen N. Allen,§ Steven C. Almo,% Richard N. Armstrong,¥ Patricia C. Babbitt,@ John E. Cronan,!,# Debra Dunaway-Mariano,∇ Heidi J. Imker,! Matthew P. Jacobson,Ë Wladek Minor,Æ C. Dale Poulter,+ Frank M. Raushel,² Andrej Sali,@ Brian K. Shoichet,Ë and Jonathan V. Sweedler!,³ Departments of Biochemistry and Chemistry and !Institute for Genomic Biology, University of Illinois, Urbana, Illinois 61801, United States §Department of Chemistry, Boston University, Boston, Massachusetts 02215, United States %Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, United States ¥Department of Biochemistry, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States @Department of Bioengineering and Therapeutic Sciences and Department of Pharmaceutical Chemistry, California Institute of Quantitative Biosciences, University of California, San Francisco, California 94143, United States #Departments of Microbiology and Biochemistry, University of Illinois, Urbana, Illinois 61801, United States ∇Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, New Mexico 87131, United States ËDepartment of Pharmaceutical Chemistry, University of California, San Francisco, California 94143, United States ÆDepartment of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia 22908, United States +Department of Chemistry, University of Utah, Salt Lake City, Utah 84112, United States ²Department of Chemistry, Texas A&M University, College Station, Texas 77843, United States ³Department of Chemistry, University of Illinois, Urbana, Illinois 61801, United States ABSTRACT: The Enzyme Function Initiative (EFI) was recently established to address the challenge of assigning reliable functions to enzymes discovered in bacterial genome projects; in this Current Topic, we review the structure and operations of the EFI.
    [Show full text]
  • The Evolution of Enzyme Function in the Isomerases
    Available online at www.sciencedirect.com ScienceDirect The evolution of enzyme function in the isomerases 1 2 Sergio Martinez Cuesta , Nicholas Furnham , 1 3 1 Syed Asad Rahman , Ian Sillitoe and Janet M Thornton The advent of computational approaches to measure functional chemical reaction is often changed by recruiting different similarity between enzymes adds a new dimension to existing catalytic residues within an active site, whilst conserving a evolutionary studies based on sequence and structure. This few residues required for the catalysis of at least one paper reviews research efforts aiming to understand the mechanistic step of the overall reaction [5]. Similarly, evolution of enzyme function in superfamilies, presenting a binding different substrates is commonly achieved by novel strategy to provide an overview of the evolution of changing the residues involved in substrate binding enzymes belonging to an individual EC class, using the and conserving residues involved in the overall reaction isomerases as an exemplar. [6]. There is substantial evidence supporting changes of Addresses the overall chemical reaction [7], as well as results report- 1 European Molecular Biology Laboratory, European Bioinformatics ing the importance of binding different substrates in the Institute EMBL-EBI, Wellcome Trust Genome Campus, Hinxton, evolution of function in superfamilies [8 ,9 ,10 ]. Com- Cambridge, CB10 1SD, United Kingdom 2 monly, enzyme superfamilies evolve by a combination of Department of Pathogen Molecular Biology, London School of Hygiene these two strategies [11,12]. For instance, phosphate & Tropical Medicine, Keppel Street, London, WC1E 7HT, United Kingdom binding sites are often conserved, whilst the rest of the 3 Institute of Structural and Molecular Biology, Division of Biosciences, substrate can be changed during evolution [13,14].
    [Show full text]
  • Inactivation of Mandelate Racemase by 3-Hydroxypyruvate Reveals a Potential Mechanistic Link Between Enzyme Superfamilies Mitesh Nagar Dalhousie University
    Marquette University e-Publications@Marquette Biological Sciences Faculty Research and Biological Sciences, Department of Publications 5-5-2015 Inactivation of Mandelate Racemase by 3-Hydroxypyruvate Reveals a Potential Mechanistic Link between Enzyme Superfamilies Mitesh Nagar Dalhousie University Brittney N. Wyatt Marquette University Martin St. Maurice Marquette University, [email protected] Stephen L. Bearne Dalhousie University Accepted version. Biochemistry, Vol. 54, No. 17 (May 5, 2015): 2747-2757. DOI. © 2015 American Chemical Society. Used with permission. NOT THE PUBLISHED VERSION; this is the author’s final, peer-reviewed manuscript. The published version may be accessed by following the link in the citation at the bottom of the page. Inactivation of Mandelate Racemase by 3-Hydroxypyruvate Reveals a Potential Mechanistic Link between Enzyme Superfamilies Mitesh Nagar Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Canada Brittney N. Wyatt Department of Biological Sciences, Marquette University, Milwaukee, WI Martin St. Maurice Department of Biological Sciences, Marquette University, Milwaukee, WI Stephen L. Bearne Department of Biochemistry and Molecular Biology, Department of Chemistry, Dalhousie University, Halifax, Canada Biochemistry, Vol 54, No. 17 (May 5, 2015): pg. 2747-2757. DOI. This article is © American Chemical Society and permission has been granted for this version to appear in e-Publications@Marquette. American Chemical Society does not grant permission for this article to be further copied/distributed or hosted elsewhere without the express permission from American Chemical Society. 1 NOT THE PUBLISHED VERSION; this is the author’s final, peer-reviewed manuscript. The published version may be accessed by following the link in the citation at the bottom of the page.
    [Show full text]
  • Divergent Evolution in the Enolase Superfamily: the Interplay of Mechanism and Specificityq
    ABB Archives of Biochemistry and Biophysics 433 (2005) 59–70 www.elsevier.com/locate/yabbi Minireview Divergent evolution in the enolase superfamily: the interplay of mechanism and specificityq John A. Gerlta,*, Patricia C. Babbittb, Ivan Raymentc a Departments of Biochemistry and Chemistry, University of Illinois, Urbana, IL 61801, USA b Departments of Biopharmaceutical Sciences and Pharmaceutical Chemistry, University of California, San Francisco, CA 94143, USA c Department of Biochemistry, University of Wisconsin, Madison, WI 53705, USA Received 22 June 2004, and in revised form 15 July 2004 Available online 9 September 2004 Abstract The members of the mechanistically diverse enolase superfamily catalyze different overall reactions. Each shares a partial reaction in which an active site base abstracts the a-proton of the carboxylate substrate to generate an enolate anion intermediate that is stabilized by coordination to the essential Mg2+ ion; the intermediates are then directed to different products in the different active sites. In this minireview, our current understanding of structure/function relationships in the divergent members of the superfamily is reviewed, and the use of this knowledge for our future studies is proposed. Ó 2004 Published by Elsevier Inc. Keywords: Enolase superfamily; Divergent evolution In 1990, the structure-based discovery was made that: mediate are highly conserved [1]. The enzymes share a (1) the three-dimensional structures of mandelate race- bidomain structure, in which the active sites are located mase (MR)1 from Pseudomonas putida and muconate at the interface between flexible loops in a capping do- lactonizing enzyme (MLE), also from P. putida, are main formed from segments contributed by the N- and remarkably superimposable (Fig.
    [Show full text]
  • Glucdrp) and L-Lyxonate Dehydratase Proteins (Lyxd)
    MINING THE ENOLASE SUPERFAMILY FOR NEW FUNCTIONS: INVESTIGATIONS OF D-GLUCARATE DEHYDRATASE RELATED PROTEINS (GLUCDRP) AND L-LYXONATE DEHYDRATASE PROTEINS (LYXD) BY SALEHE GHASEM PUR DISSERTATION Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biochemistry in the Graduate College of the University of Illinois at Urbana-Champaign, 2014 Urbana, Illinois Doctoral Committee: Professor John A. Gerlt, Chair Professor Wilfred A. van der Donk Professor James H. Morrissey Professor Emad Tajkhorshid ABSTRACT Genomic era begins with development of sequencing methods. Genome sequencing is now cost-effective and fast, giving rise to increasing amounts of genomic data. However, the function of 1% of the deposited sequences have been experimentally characterized. There is no robust method of functional assignment for these sequences. Functional assignments are now performed using a variety of software tools to utilize the known biochemical data of characterized proteins to annotate similar sequences in genome databases. With this large scale automatic annotations of genome databases, annotations were transferred from homologs regardless of their reliability which result in propagation of errors and transfer misleading information to scientific community. Nevertheless, annotating the homologs within a superfamily is a valid approach. To this end, the enolase superfamily is an excellent model system for functional assignment. Structurally, this superfamily contain substrate specificity residues in the N-terminal capping domain and catalytic residues in the C-terminal barrel domain. These proteins with the common structural fold have the ability to abstract a proton α to carboxylate on the substrate before proceeding to dehydration, epimerization, deamination, racemization or cycloisomerization.
    [Show full text]