DOCSLIB.ORG

Reducible Crosslinks in Hydroxylysine-Deficient Collagens of a Heritable Disorder of Connective Tissue (Skin/Bone/Cartilage/Aminoacid Analysis)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Reducible Crosslinks in Hydroxylysine-Deficient Collagens of a Heritable Disorder of Connective Tissue (Skin/Bone/Cartilage/Aminoacid Analysis) Proc. Nat. Acad. Sci. USA Vol. 69, No. 9, pp. 2594-2598, September 1972 Reducible Crosslinks in Hydroxylysine-Deficient Collagens of a Heritable Disorder of Connective Tissue (skin/bone/cartilage/aminoacid analysis) DAVID R. EYRE AND MELVIN J. GLIMCHER* Department of Orthopedic Surgery, Harvard Medical School, Children's Hospital Medical Center, Boston, Massachusetts 02115 Communicated by Francis 0. Schmitt, July 3, 1972 ABSTRACT Reducible compounds that participate don, bone, and cartilage collagens (3-11). Each tissue reveals in crosslinking were analyzed in hydroxylysine-deficient a unique distribution of these reducible crosslinks that changes collagens of patients with a heritable disorder of connec- tive tissue. After treatment with [3H1sodium borohydride, as the tissue matures and ages (8, 10). new compounds, as well as a totally different pattern of Since connective tissues of patients with this disorder are tritiated compounds, were found in hydroxylysine-de- deficient in hydroxylysine, a crosslink precursor, it seemed ficient collagen from skin as compared with age-matched likely that the reducible crosslinks would either be absent or controls. The amount of desmosines detected indicated collagen cross- that more elastin was present in abnormal skin than in abnormal. Such a deficiency or abnormality in control skin. linking might be responsible for changes in the solubility Bone collagen, which was not as deficient in hydroxy- characteristics of the collagen (1), and for changes in the lysine as skin collagen, had the same compounds as normal structural properties of the tissues and the consequent skeletal bone collagen, but their relative proportions were altered, and connective tissue abnormalities. consistent with a deficiency of hydroxylysine, a precursor of the crosslinks. Although the content of hydroxylysine Biopsies of skin, bone, and cartilage removed during sur- in collagen of cartilage is essentially normal in these pa- gery were analyzed for the reducible components of collagen, tients, analysis after reduction revealed a different pat- and the results were compared to those obtained from the tern of reduced compounds from that of normal cartilage. It is speculated that Type II collagen, the major collagen component in cartilage, contains a normal amount of hydroxylysine, while Type I collagen, which is the major source of the crosslinks, is hydroxylysine-deficient. This Hydroxyysine - Defitient Skin distribution would explain the findings of an abnormal profile of reducible compounds despite an almost normal total hydroxylysine content. The finding that the deficiency of hydroxylysine in the 5 _ collagen of these patients is accompanied by changes in number, chemical nature, and, probably, distribution of ? crosslinkages, and the previously reported alterations in the solubility characteristics, suggest that at least some skeletal and connective tissue abnormalities are directly related to underlying molecular pathology. I.. 4 r Control SkinPost-Histt. Aminoacid analyses of biopsies from two siblings with a heri- -4 V~~~~~~~~~~~LNL table disorder of connective tissue revealed the presence of '4.. hydroxylysine-deficient collagen (1). Hydroxylysine was '4.. present in skin collagen at about 5% of the amount found in collagen of normal skin, and at higher, but still markedly reduced, amounts in fascia and bone, while the content in 4 Control Skin 'Post-Iistidinen amount. The basic cartilage was about 90% of the normal 14,4~HLNL~~~~~~~~ biochemical defect is an abnormally low activity of the en- zyme lysyl-protocollagen hydroxylase in cells that synthesize I0Z,0 collagen in the affected connective tissues (2). Hydroxylysine is a precursor in the biosynthesis of certain collagen crosslinks (3, 4). Borohydride-reducible crosslinks, which are apparently intermediates in the biosynthesis of more stable bonds, have been identified in normal skin, ten- 00 20 40 60 80 100 120 140 160 180 200 FRACTION NUMBER Abbreviations: HLNL, hydroxylysinonorleucine; HLHNL, hy- FIG. 1. Comparison of the elution profiles of tritiated com- droxylysinohydroxylnorleucine; DHNL, dihydroxynorleucine. pounds in hydrolysates of normal and hydroxylysine-deficient * Reprint requests to: Melvin J. Glimcher, M.D., Department of human skin collagens treated with [3H]borohydride. 10 mg dry Orthopedic Surgery, Children's Hospital Medical Center, 300 weight of each material were hydrolyzed in acid and applied Longwood Ave., Boston, Mass. 02115. to the aminoacid analyzer. HLNL, hydroxylysinonorleucine. 2594 Downloaded by guest on September 30, 2021 Proc. Nat. Acad. Sci. USA 69 (1972) Crosslinks in Hydroxylysine-Deficient Collagens 2595 collagens of site-matched and age-matched samples of normal Hydroxylysine- Deficient Skin tissues. METHODS Skin biopsies were scraped free of fat and stirred in 2 M NaBr for several hours to facilitate removal of epidermis (1). The dermis was washed thoroughly by stirring in saline and then water at 4°. Samples of cortical bone from spinous processes of thoracic vertebrae were washed by stirring in saline and then demineralized in 0.2 M EDTA (pH 7.9), at 40 for several days, followed by further washing in distilled water. Rib cartilage was stirred in saline and then water. Control Skin Samples of the washed tissues were cut into small pieces, HIS stirred in 0.1 M sodium phosphate (pH 7.4), and reacted with tritiated sodium borohydride (10 Ci/mol) at room tem- perature (250) for 45 min. Acetic acid was added to bring the solution to pH 3.0, and after 5 min of further stirring, the tissue pieces were thoroughly washed in several changes of distilled water. After the tissue was dried over P205, it was hydrolyzed in 3 N HCl in an evacuated, sealed tube for 48 hr at 1050, conditions that prevent certain participants of crosslinking from being destroyed (12). Amino acids were I_e--- r-------?- . fractionated on an aminoacid analyzer equipped for stream 155 160 165 170 175 180 splitting. Tritium activity was measured in a portion of the FRACTION NUMBER column effluent, and radioactive peaks were identified as described (13). FIG. 2. Regions of the two chromatograms depicted in Fig. 1 Site-matched and age-matched samples of skin, bone, and comparing the elution profiles of tritium activity and of ninhy- cartilage were taken at biopsy or autopsy from normal con- drin-positive material. - , absorbance at 570 nm; nective tissues and analyzed by the same procedures. 'H activity. RESULTS from the abnormal skin collagen eluted from the column later Skin than the major radioactive peak found in normal skin collagen, The elution profile of tritiated compounds from a hydrolysate indicating they were not the same compounds. of reduced collagen of abnormal skin was markedly different The radioactive peak eluting at fraction number 130 was from that of normal skin (Fig. 1). Three independent age- also of interest. This peak was much larger in borohydride- matched samples of normal skin revealed essentially the treated samples of diseased skin than in normal skin. It eluted same patterns. Skin biopsies from each of the two siblings in an identical position to the reduced desmosine peak from with the disease gave virtually the same abnormal elution a hydrolysate of reduced elastin. Identification as reduced profiles of tritium activity. The major peak from normal desmosine on this basis alone was not reliable since several skin collagen was apparently the material described as post- minor radioactive peaks also eluted in this region on analysis histidine compound (14, 15) or Fraction C (6, 9, 10). The of bone collagen. However, conventional aminoacid analysis, next most abundant compound was hydroxylysinonorleucine by reaction with ninhydrin, of a hydrolysate of a relatively (HLNL), derived by reduction of the aldimine crosslink, large sample (10 mg dry weight) of dermis, which had not dehydrohydroxylysinonorleucine, formed by addition between been treated with borohydride, confirmed that more of the a residue of hydroxylysine and a residue of allysine, the alde- elastin crosslinks, desmosine and isodesmosine, were present hyde from an enzymic oxidative deamination of a lysyl res- in abnormal skin than in a sample of control skin. There idue. The abnormal skin, however, did not reveal any of appeared to be four times the concentration of desmosines the normal "post-histidine" compound, and HLNL was per unit weight of collagen in one of the samples of diseased much diminished and possibly absent since its elution posi- skin compared to normal skin. Collagen was estimated by tion was now obscured by several minor peaks. Instead, a hydroxyproline content. new major peak of tritium activity eluted later than the normal "post-histidine" peak, and appeared as a partially Bone resolved double peak suggesting that more than one com- The hydroxylysine content of samples of diseased bone varied pound was present. A ninhydrin-positive double peak coin- considerably. Spongy bone from the interior of a vertebra cided precisely with the radioactive peak (Fig. 2). In terms of contained collagen with about 50% of the normal amount of lysine equivalents, this double peak represented in total one hydroxylysine (1). However, histological examination after to two lysine residues per molecule, or about 0.5 lysine res- staining with Safranin 0 showed that pockets of cartilage idue per a chain. It was not detected in the collagen without were included in the bone sample. In the present study, corti- prior borohydride treatment, indicating that the
Load more

Recommended publications
  • Collagen and Elastin Fibres
    J Clin Pathol: first published as 10.1136/jcp.s3-12.1.49 on 1 January 1978. Downloaded from J. clin. Path., 31, Suppl. (Roy. Coll. Path.), 12, 49-58 Collagen and elastin fibres A. J. BAILEY From the Agricultural Research Council, Meat Research Institute, Langford, Bristol Although an understanding of the intracellular native collagen was generated from type I pro- biosynthesis of both collagen and elastin is of collagen. Whether this means that the two pro- considerable importance it is the subsequent extra- collagens are converted by different enzyme systems cellular changes involving fibrogenesis and cross- and the type III enzyme was deficient in these linking that ensure that these proteins ultimately fibroblast cultures, or that the processing of pro become the major supporting tissues of the body. type III is extremely slow, is not known. The latter This paper summarises the formation and stability proposal is consistent with the higher proportion of collagen and elastin fibres. of soluble pro type III extractable from tissue (Lenaers and Lapiere, 1975; Timpl et al., 1975). Collagen Basement membrane collagens, on the other hand, do not form fibres and this property may be The non-helical regions at the ends of the triple due to the retention of the non-helical extension helix of procollagen probably provide a number of peptides (Kefalides, 1973). In-vivo biosynthetic different intracellular functions-that is, initiating studies showing the absence of any extension peptide rapid formation of the triple helix; inhibiting intra- removal support this (Minor et al., 1976), but other cellular fibrillogenesis; and facilitating transmem- workers have reported that there is some cleavage brane movement.
    [Show full text]
  • 01. Amino Acids
    01. Amino Acids 1 Biomolecules • Protein • Carbohydrate • Nucleic acid • Lipid 2 peptide polypeptide protein di-, tri-, oligo- 3 4 fibrous proteins proteins globular proteins 5 Figure 4.1 Anatomy of an amino acid. Except for proline and its derivatives, all of the amino acids commonly found in proteins possess this type of structure. 6 Glycine (Gly, G) Alanine (Ala, A) Valine (Val, V)* Leucine (Leu, L)* Isoleucine (Ile. I)* 7 Serine (Ser, S) Threonine (Thr, T)* Cysteine (Cys, C)cystine Methionine (Met, M)* 8 Aspartate (Asp, D) Glutamate (Glu, E) Asparagine (Asn, N) Glutamine (Gln, Q) 9 Lysine (Lys, K)* Arginine (Arg, R)* 10 Phenylalanine (Phe, F)* Tyrosine (Tyr, Y) Histidine (His, H)* Tryptophan (Trp, W)* 11 Proline (Pro, P) 12 Hydrophobic (A, G, I, L, F, V, P) Hydrophilic (D, E, R, S, T, C, N, Q, H) Amphipathic (K, M, W, Y) 13 Essential amino acids: V, L, I, T, M, K, R, F, H, W 14 Several Amino Acids Occur Rarely in Proteins We'll see some of these in later chapters • Selenocysteine in many organisms • Pyrrolysine in several archaeal species • Hydroxylysine, hydroxyproline - collagen • Carboxyglutamate - blood-clotting proteins • Pyroglutamate – in bacteriorhodopsin • GABA, epinephrine, histamine, serotonin act as neurotransmitters and hormones • Phosphorylated amino acids – a signaling device Several Amino Acids Occur Rarely in Proteins Several Amino Acids Occur Rarely in Proteins Figure 4.4 (b) Some amino acids are less common, but nevertheless found in certain proteins. Hydroxylysine and hydroxyproline are found in connective-tissue proteins; carboxy- glutamate is found in blood-clotting proteins; pyroglutamate is found in bacteriorhodopsin (see Chapter 9).
    [Show full text]
  • Collagen Structural Microheterogeneity and a Possible Role for Glycosylated Hydroxylysine in Type 1 Collagen
    Proc. NatL Acad. Sci. USA Vol. 79, pp. 7684-7688, December 1982 Biochemistry Collagen structural microheterogeneity and a possible role for glycosylated hydroxylysine in type 1 collagen (nonreducible stable crosslinks/hydroxyaldolhistidine/specific cleavage/molecular location) MITSUO YAMAUCHI*t, CLAUDIA NOYES*t, YOSHINORI KUBOKI*t, AND GERALD L. MECHANIC*§¶ *Dental Research Center, §Department of Biochemistry and Nutrition, and tDepartment of Medicine, University of North Carolina, Chapel Hill, North Carolina 27514 Communicated by. Ernest L. Eliel, September 20, 1982 ABSTRACT A three-chained peptide from type I collagen, and Mechanic (8) that dehydro-HisOHMerDes, which was crosslinked by hydroxyaldolhistidine, has been isolated from a thought to be artifactual (9, 10) is a true crosslink in collagen tryptic digest of5 M guanidine HCI-insoluble bovine skin collagen fibrils. Bernstein and Mechanic found that one HisOHMerDes (a small but as yet unknown percentage of the total collagen in crosslink was present per molecule of collagen in freshly re- whole skin). Os04/NaIO4 specifically cleaved the crosslink at its constituted soluble collagen fibrils. double bond into a two-chained crosslink peptide and a single pep- Histidine was also found to be a constituent of the stable tide. The sequence of the two-chained peptide containing the bi- nonreducible trifunctional crosslink hydroxyaldolhistidine functional crosslink was determined after amino acid analysis of (OHAlHis), whose structure was elucidated by PMR and mass the separated peptides. The crosslink consists of an aldehyde de- spectrometry rived from hydroxylysine-87 in the aldehyde-containing cyanogen (11). OHAIHis was isolated from bovine skin col- bromide fragment alCB5ald and an aldehyde derived from the lagen.
    [Show full text]
  • United States Patent (19) 11 Patent Number: 5,874,589 Campbell Et Al
    USOO5874589A United States Patent (19) 11 Patent Number: 5,874,589 Campbell et al. 45) Date of Patent: Feb. 23, 1999 54 METHODS FOR SYNTHESIZING DIVERSE El Marini et al., 1992, Synthesis pp. 1104-1108 Synthesis of COLLECTIONS OF TETRAMIC ACIDS AND enantiomerically pure B-and Y-amino acids from aspartic DERVATIVES THEREOF and glutamic acid derivatives. Evans et al., 1982, J. Amer. Chem. Soc. 104: 1737–1739 75 Inventors: David A. Campbell, San Mateo; Todd Asymmetric alkylation reactions of chiral imide enolates. A T. Romoff, San Jose, both of Calif. practical approach to the enantioselective Synthesis of C-Substituted carboxylic acid derivatives. 73 Assignee: GlaxoWellcome, Inc., Research Fontenot et al., 1991, Peptide Research, 4: 19-25A Survey Triangle Park, N.C. of potential problems and qulaity control in peptide Synthe sis by the flourenylmethocvarbonyl procedure. 21 Appl. No.: 896,799 Giesemann et al., 1982, J. Chem. Res. (S) pp. 79 Synthesis 22 Filed: Jul.18, 1997 of chiral C-isocyano esters and other base-Sensitive isocya nides with 51) Int. Cl. ........................ C07D 211/40; CO7D 207/00 oxomethylenebis-(3H-Imidazolium)Bis(methanesulphonate), 52 U.S. Cl. ............ ... 548/540; 546/220; 548/539 a versatile dehydrating reagent. 58 Field of Search ............................. 546/220; 548/539, Geysen et al., 1987, J. Immunol. Meth. 102: 259-274 548/540 Strategies for epitope analysis using peptide Synthesis. Giron-Forest et al., 1979, Analytical Profiles of Drug Sub 56) References Cited stances, 8: 47-81 Bromocriptine methaneSulphonate. U.S. PATENT DOCUMENTS Gokeletal, 1971, Isonitrile Chemistry, Ugi, I. ed., Academic 3,299.095 1/1967 Harris et al.
    [Show full text]
  • Ihyd-Pseaac: Predicting Hydroxyproline and Hydroxylysine in Proteins by Incorporating Dipeptide Position-Specific Propensity Into Pseudo Amino Acid Composition
    Int. J. Mol. Sci. 2014, 15, 7594-7610; doi:10.3390/ijms15057594 OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 www.mdpi.com/journal/ijms Article iHyd-PseAAC: Predicting Hydroxyproline and Hydroxylysine in Proteins by Incorporating Dipeptide Position-Specific Propensity into Pseudo Amino Acid Composition Yan Xu 1,5,*, Xin Wen 1, Xiao-Jian Shao 2, Nai-Yang Deng 3 and Kuo-Chen Chou 4,5 1 Department of Information and Computer Science, University of Science and Technology Beijing, Beijing 100083, China; E-Mail: [email protected] 2 Department of Mathematics and Information Science, Binzhou University, Binzhou 256603, China; E-Mail: [email protected] 3 College of Science, China Agricultural University, Beijing 100083, China; E-Mail: [email protected] 4 Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah 21589, Saudi Arabia; E-Mail: [email protected] 5 Gordon Life Science Institute, Boston, MA 02478, USA * Author to whom correspondence should be addressed; E-Mail: [email protected] or [email protected]; Tel./Fax: +86-10-6233-2589. Received: 7 February 2014; in revised form: 4 April 2014 / Accepted: 17 April 2014 / Published: 5 May 2014 Abstract: Post-translational modifications (PTMs) play crucial roles in various cell functions and biological processes. Protein hydroxylation is one type of PTM that usually occurs at the sites of proline and lysine. Given an uncharacterized protein sequence, which site of its Pro (or Lys) can be hydroxylated and which site cannot? This is a challenging problem, not only for in-depth understanding of the hydroxylation mechanism, but also for drug development, because protein hydroxylation is closely relevant to major diseases, such as stomach and lung cancers.
    [Show full text]
  • Lysyl-Protocollagen Hydroxylase Deficiency in Fibroblasts from Siblings with Hydroxylysine-Deficient Collagen
    Proc. Nat. Acad. Sci. USA Vol. 69, No. 10, pp. 2899-2903, October 1972 Lysyl-Protocollagen Hydroxylase Deficiency in Fibroblasts from Siblings with Hydroxylysine-Deficient Collagen (prolyl-protocollagen hydroxylase/connective tissue/inborn error/crosslinks) S. M. KRANE, S. R. PINNELL, AND R. W. ERBE Departments of Medicine, Dermatology, and Pediatrics, Harvard Medical School and the Medical, Dermatology, and Children's Services, Massachusetts General Hospital, Boston, Massachusetts 02114 Communicated by E. R. Blout, July 31, 1972 ABSTRACT Cell culture studies were performed on were normal. The hydroxylysine content of dermis was also members of a family in which two sisters, ages 9 and 12, normal in three patients, each with the Marfan and Ehlers- have a similar disorder characterized clinically by severe scoliosis, joint laxity and recurrent dislocations, hyper- Danlos syndromes. Collagen from the skin of the affected extensible skin, and thin scars. The skin collagen from the children was more soluble in denaturing solvents than that sisters was markedly deficient in hydroxylysine, but other derived from controls (4), consistent with a defect in cross- amino acids were present in normal amounts. Hydroxy- linking of collagen molecules, a process in which hydroxylysine lysine in collagen from fascia and bone was reduced to a to involved lesser extent. Since the most likely explanation for the has been thought be critically (2, 5-8). Hydroxyly- hydroxylysihie deficiency was a reduction in enzymatic sine per se is not used in collagen biosynthesis; specific lysyl hydroxylation of lysine residues in protocollagen, we mea- residues are hydroxylated after their incorporation into the sured the activity of lysyl-protocollagen hydroxylase in polypeptide chains of protocollagen (9-12).
    [Show full text]
  • Lysine and Novel Hydroxylysine Lipids in Soil Bacteria: Amino Acid Membrane Lipid Response to Temperature and Ph in Pseudopedobacter Saltans
    Rowan University Rowan Digital Works School of Earth & Environment Faculty Scholarship School of Earth & Environment 6-1-2015 Lysine and novel hydroxylysine lipids in soil bacteria: amino acid membrane lipid response to temperature and pH in Pseudopedobacter saltans Elisha Moore Rowan University Ellen Hopmans W. Irene Rijpstra Irene Sanchez Andrea Laura Villanueva See next page for additional authors Follow this and additional works at: https://rdw.rowan.edu/see_facpub Part of the Environmental Microbiology and Microbial Ecology Commons Recommended Citation Moore, E.K., Hopmans, E., Rijpstra, W.I.C., Sanchez-Andrea, I., Villanueva, L., Wienk, H., ...& Sinninghe Damste, J. (2015). Lysine and novel hydroxylysine lipids in soil bacteria: amino acid membrane lipid response to temperature and pH in Pseudopedobacter saltans. Frontiers in Microbiology, Volume 6, Article 637. This Article is brought to you for free and open access by the School of Earth & Environment at Rowan Digital Works. It has been accepted for inclusion in School of Earth & Environment Faculty Scholarship by an authorized administrator of Rowan Digital Works. Authors Elisha Moore, Ellen Hopmans, W. Irene Rijpstra, Irene Sanchez Andrea, Laura Villanueva, Hans Wienk, Frans Schoutsen, Alfons Stams, and Jaap Sinninghe Damsté This article is available at Rowan Digital Works: https://rdw.rowan.edu/see_facpub/17 ORIGINAL RESEARCH published: 29 June 2015 doi: 10.3389/fmicb.2015.00637 Lysine and novel hydroxylysine lipids in soil bacteria: amino acid membrane lipid response to temperature and pH in Pseudopedobacter saltans Eli K. Moore 1*, Ellen C. Hopmans 1, W. Irene C. Rijpstra 1, Irene Sánchez-Andrea 2, Laura Villanueva 1, Hans Wienk 3, Frans Schoutsen 4, Alfons J.
    [Show full text]
  • Biochemistry Centennial Celebration 1915 - 2015
    BIOCHEMISTRY CENTENNIAL CELEBRATION 1915 - 2015 FEATURED SPEAKERS Dr. Hung-Ying Kao (Ph.D., 1995) Dr. Rebecca Moen (Ph.D., 2013) Professor of Biochemistry Assistant Professor of Chemistry & Geology Case Western Reserve University | Cleveland, OH Minnesota State University | Mankato, MN Dr. Venkateswarlu Pothapragada (Ph.D., 1962) Dr. Amy Rocklin (Ph.D., 2000) Division Scientist, 3M | Minneapolis-St. Paul, MN Corning, Inc. | Painted Post, NY Dr. Melanie Simpson (Ph.D., 1997) Dr. Brad Wallar (Ph.D., 2000) Professor of Biochemistry Associate Professor of Chemistry University of Nebraska | Lincoln, NE Grand Valley State University | Allendale, MI Thursday, May 14, 2015, 1:00-5:30 PM 2-470 Phillips-Wangensteen Building Minneapolis Campus Sponsored by The Frederick James Bollum Endowed Research Fund for Biochemistry NIVERSITY OF INNESOTA _____________________________________________________________________________________________U M Twin Cities Campus Department of Biochemistry, 6-155 Jackson Hall Molecular Biology and Biophysics 321 Church St. SE Minneapolis, MN, 55455 Medical School and V: (612) 625-6100 College of Biological Sciences F: (612) 625-2163 http://www.cbs.umn.edu/bmbb May 14, 2015 Dear Friends; Welcome to the Centennial Celebration commemorating the 100th anniversary of the first PhD granted in biochemistry at the University of Minnesota. Morris J. Blish was our first PhD recipient and he went on to a marvelously distinguished career in the food industry and was recognized by the U of MN in 1952 by President Morrill with the Outstanding
    [Show full text]
  • Proposal of the Annotation of Phosphorylated Amino Acids and Peptides Using Biological and Chemical Codes
    molecules Article Proposal of the Annotation of Phosphorylated Amino Acids and Peptides Using Biological and Chemical Codes Piotr Minkiewicz * , Małgorzata Darewicz , Anna Iwaniak and Marta Turło Department of Food Biochemistry, University of Warmia and Mazury in Olsztyn, Plac Cieszy´nski1, 10-726 Olsztyn-Kortowo, Poland; [email protected] (M.D.); [email protected] (A.I.); [email protected] (M.T.) * Correspondence: [email protected]; Tel.: +48-89-523-3715 Abstract: Phosphorylation represents one of the most important modifications of amino acids, peptides, and proteins. By modifying the latter, it is useful in improving the functional properties of foods. Although all these substances are broadly annotated in internet databases, there is no unified code for their annotation. The present publication aims to describe a simple code for the annotation of phosphopeptide sequences. The proposed code describes the location of phosphate residues in amino acid side chains (including new rules of atom numbering in amino acids) and the diversity of phosphate residues (e.g., di- and triphosphate residues and phosphate amidation). This article also includes translating the proposed biological code into SMILES, being the most commonly used chemical code. Finally, it discusses possible errors associated with applying the proposed code and in the resulting SMILES representations of phosphopeptides. The proposed code can be extended to describe other modifications in the future. Keywords: amino acids; peptides; phosphorylation; phosphate groups; databases; code; bioinformatics; cheminformatics; SMILES Citation: Minkiewicz, P.; Darewicz, M.; Iwaniak, A.; Turło, M. Proposal of the Annotation of Phosphorylated Amino Acids and Peptides Using 1. Introduction Biological and Chemical Codes.
    [Show full text]
  • Metabolic Profiling Detects Biomarkers of Protein Degradation in COPD Patients
    Metabolic profiling detects biomarkers of protein degradation in COPD patients On‐line data supplement Baljit K. Ubhi, John H. Riley, Paul A. Shaw, David A. Lomas, Ruth Tal-Singer, William MacNee, Jules L Griffin, Susan C Connor Materials and Methods: ECLIPSE is a 3 year longitudinal study with samples collected at baseline, 3 and 6 months and then every 6 months for 3 years. Control subjects consisting of current or former smokers and individuals who have never smoked (n=566), were recruited as comparators with the COPD subjects (2756). The COPD patients were selected according to the following criteria; an forced expiratory volume in the first second (FEV1) of less than 80% of predicted normal and a baseline FEV1/ forced vital capacity(FVC) ratio of less than 0.7, aged 40-75 and either current or ex-smokers with a greater than 10 pack-year history. Patients were categorised according to the criteria from the Global Initiative for Chronic Obstructive Lung Disease (GOLD status; (E1)) i.e. COPD patients had an FEV1/FVC ratio of less than 70% and were subdivided into GOLD stage II, stage III and stage IV based on an 50%<FEV1<80%, 30%<FEV1<50% and <30% FEV1 predicted respectively. The control group consists of a cohort of 343 current and ex-smokers with greater than 10 pack-year smoking history and a second cohort of 223 who have never smoked (less than 1 pack-year smoking history). Both cohorts that make up the control groups have a baseline FEV1 greater than 85% predicted and a FEV1/FVC ratio of greater than 0.7.
    [Show full text]
  • Properties and Units in the Clinical Laboratory Sciences Part X
    Pure Appl. Chem., Vol. 72, No. 5, pp. 747–972, 2000. © 2000 IUPAC INTERNATIONAL FEDERATION OF CLINICAL CHEMISTRY AND LABORATORY MEDICINE SCIENTIFIC DIVISION COMMITTEE ON NOMENCLATURE, PROPERTIES AND UNITS (C-NPU)# and INTERNATIONAL UNION OF PURE AND APPLIED CHEMISTRY CHEMISTRY AND HUMAN HEALTH DIVISION CLINICAL CHEMISTRY SECTION COMMISSION ON NOMENCLATURE, PROPERTIES AND UNITS (C-NPU)§ PROPERTIES AND UNITS IN THE CLINICAL LABORATORY SCIENCES PART X. PROPERTIES AND UNITS IN GENERAL CLINICAL CHEMISTRY (Technical Report) (IFCC–IUPAC 1999) Prepared for publication by HENRIK OLESEN1, INGE IBSEN1, IVAN BRUUNSHUUS1, DESMOND KENNY2, RENÉ DYBKÆR3, XAVIER FUENTES-ARDERIU4, GILBERT HILL5, PEDRO SOARES DE ARAUJO6, AND CLEM McDONALD7 1Office of Laboratory Informatics, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark; 2Dept. of Clinical Biochemistry, Our Lady’s Hospital for Sick Children, Dublin, Ireland; 3Dept. of Standardisation in Laboratory Medicine, Kommunehospitalet, Copenhagen, Denmark; 4Dept. of Clinical Biochemistry, Ciutat Sanitària i Universitària de Bellvitge, Barcelona, Spain; 5Dept. of Clinical Chemistry, Hospital for Sick Children, Toronto, Canada; 6Dept. of Biochemistry, IQUSP, São Paolo, Brazil; 7Regenstrief Inst. for Health Care, Indiana University School of Medicine, Indianapolis, Indiana, USA #§The combined Memberships of the Committee and the Commission (C-NPU) during the preparation of this report (1994 to 1996) were as follows: Chairman: H. Olesen (Denmark, 1989–1995); D. Kenny (Ireland, 1996). Members: X. Fuentes-Arderiu (Spain, 1991–1997); J. G. Hill (Canada; 1987–1997); D. Kenny (Ireland, 1994–1997); H. Olesen (Denmark, 1985–1995); P. L. Storring (UK, 1989–1995); P. Soares de Araujo (Brazil, 1994–1997); R. Dybkær (Denmark, 1996–1997); C. McDonald (USA, 1996–1997). Please forward comments to: H.
    [Show full text]
  • WO 2010/037397 Al
    (12) INTERNATIONALAPPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date 8 April 2010 (08.04.2010) WO 2010/037397 Al (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 38/17 (2006.01) C07K 14/705 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K 47/48 (2006.01) GOlN 33/50 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, (21) International Application Number: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/DK2009/050257 HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, (22) International Filing Date: KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, 1 October 2009 (01 .10.2009) ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, (25) Filing Language: English SE, SG, SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR, TT, (26) Publication Language: English TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every PA 2008 0 1381 1 October 2008 (01 .10.2008) DK kind of regional protection available): ARIPO (BW, GH, 61/101,898 1 October 2008 (01 .10.2008) US GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, (71) Applicant (for all designated States except US): DAKO TM), European (AT, BE, BG, CH, CY, CZ, DE, DK, EE, DENMARK A/S [DK/DK]; Produktionsvej 42, DK-2600 ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, Glostrup (DK).
    [Show full text]