Home LiteratureArticle Details
PMID: 11296285 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Prediction of protein deamidation rates from primary and three-dimensional structure.

Robinson NE, Robinson AB

Abstract

A method for the quantitative estimation of instability with respect to deamidation of the asparaginyl (Asn) residues in proteins is described. The procedure involves the observation of several simple aspects of the three-dimensional environment of each Asn residue in the protein and a calculation that includes these observations, the primary amino acid residue sequence, and the previously reported complete set of sequence-dependent rates of deamidation for Asn pentapeptides. This method is demonstrated and evaluated for 23 proteins in which 31 unstable and 167 stable Asn residues have been reported and for 7 unstable and 63 stable Asn residues that have been reported in 61 human hemoglobin variants. The relative importance of primary structure and three-dimensional structure in Asn deamidation is estimated.

MeSH Terms
Amides/chemistry Amino Acid Sequence Kinetics Molecular Sequence Data Protein Conformation Proteins/chemistry
Chemicals
Amides Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Robinson N E
Division of Chemistry, California Institute of Technology, Pasadena, CA 91125, USA.
Robinson A B
References (73)
73 references, click to expand
  1. Deamidation of HPr, a phosphocarrier protein of the phosphoenolpyruvate:sugar phosphotransferase system, involves asparagine 38 (HPr-1) and asparagine 12 (HPr-2) in isoaspartyl acid formation.
    J Biol Chem. 1993 Aug 25;268(24):17695-704 PMID: 8349654
  2. On the molecular origin of charge heterogeneity of rat liver fatty acid-binding protein (Z-protein).
    Arch Biochem Biophys. 1994 Feb 15;309(1):81-4 PMID: 8117116
  3. The high-resolution structure of the histidine-containing phosphocarrier protein HPr from Escherichia coli determined by restrained molecular dynamics from nuclear magnetic resonance nuclear Overhauser effect data.
    J Mol Biol. 1994 Apr 15;237(5):544-59 PMID: 8158637
  4. Refined crystal structures of glucoamylase from Aspergillus awamori var. X100.
    J Mol Biol. 1994 May 13;238(4):575-91 PMID: 8176747
  5. The primary structure and properties of thioltransferase (glutaredoxin) from human red blood cells.
    Protein Sci. 1994 Mar;3(3):428-34 PMID: 8019414
  6. Crystal structure of recombinant human triosephosphate isomerase at 2.8 A resolution. Triosephosphate isomerase-related human genetic disorders and comparison with the trypanosomal enzyme.
    Protein Sci. 1994 May;3(5):810-21 PMID: 8061610
  7. Repair of spontaneously deamidated HPr phosphocarrier protein catalyzed by the L-isoaspartate-(D-aspartate) O-methyltransferase.
    J Biol Chem. 1994 Oct 7;269(40):24586-95 PMID: 7929130
  8. Deamidation of polyanion-stabilized acidic fibroblast growth factor.
    J Pharm Sci. 1995 Jan;84(1):7-11 PMID: 7536241
  9. Structure of a protein in a kinetic trap.
    Nat Struct Biol. 1995 Feb;2(2):129-38 PMID: 7749917
  10. A conserved deamidation site at Asn 2 in the catalytic subunit of mammalian cAMP-dependent protein kinase detected by capillary LC-MS and tandem mass spectrometry.
    Protein Sci. 1998 Feb;7(2):457-69 PMID: 9521123
  11. The NMR solution structure of human glutaredoxin in the fully reduced form.
    J Mol Biol. 1998 Jul 24;280(4):687-701 PMID: 9677297
  12. Posttranslational deamidation of proteins: the case of hemoglobin J Sardegna [alpha50(CD8)His-->Asn-->Asp].
    Clin Chem. 1999 Jan;45(1):21-8 PMID: 9895333
  13. Refined crystal structures of native human angiogenin and two active site variants: implications for the unique functional properties of an enzyme involved in neovascularisation during tumour growth.
    J Mol Biol. 1999 Jan 22;285(3):1209-33 PMID: 9918722
  14. The 2.0 A structure of human hypoxanthine-guanine phosphoribosyltransferase in complex with a transition-state analog inhibitor.
    Nat Struct Biol. 1999 Jun;6(6):588-93 PMID: 10360366
  15. Solution structure of reduced horse heart cytochrome c.
    J Biol Inorg Chem. 1999 Feb;4(1):21-31 PMID: 10499099
  16. Hemoglobin Wayne: a frameshift mutation detected in human hemoglobin alpha chains.
    Proc Natl Acad Sci U S A. 1976 Mar;73(3):882-6 PMID: 1062801
  17. Hemoglobin Providence. A human hemoglobin variant occurring in two forms in vivo.
    J Biol Chem. 1976 Dec 10;251(23):7557-62 PMID: 1002699
  18. Molecular basis for the accumulation of acidic isozymes of triosephosphate isomerase on aging.
    Mech Ageing Dev. 1981 Oct;17(2):151-62 PMID: 7311622
  19. Human hypoxanthine-guanine phosphoribosyltransferase. Tryptic peptides and post-translational modification of the erythrocyte enzyme.
    J Biol Chem. 1982 Dec 25;257(24):14830-4 PMID: 7174669
  20. In vitro deamidation of human triosephosphate isomerase.
    Arch Biochem Biophys. 1986 Aug 1;248(2):452-9 PMID: 3740839
  21. Deamidation of the asparaginyl-glycyl sequence.
    Int J Pept Protein Res. 1986 Jul;28(1):79-84 PMID: 3759344
  22. Deamidation, isomerization, and racemization at asparaginyl and aspartyl residues in peptides. Succinimide-linked reactions that contribute to protein degradation.
    J Biol Chem. 1987 Jan 15;262(2):785-94 PMID: 3805008
  23. Comparison of the primary structures of ribonuclease U2 isoforms.
    Biochem J. 1986 Nov 15;240(1):163-70 PMID: 3827836
  24. Selective deamidation and enzymatic methylation of seminal ribonuclease.
    Biochemistry. 1986 Dec 30;25(26):8361-8 PMID: 3828285
  25. Three-dimensional structure of interleukin-2.
    Science. 1987 Dec 18;238(4834):1707-9 PMID: 3500515
  26. Evidence for isoaspartyl (deamidated) forms of mouse epidermal growth factor.
    Anal Biochem. 1987 Sep;165(2):420-9 PMID: 3501256
  27. Tertiary structure is a principal determinant to protein deamidation.
    Science. 1988 Apr 8;240(4849):191-4 PMID: 3353715
  28. Effect of protein conformation on rate of deamidation: ribonuclease A.
    Proteins. 1989;5(1):8-12 PMID: 2748573
  29. Formation of isoaspartate at two distinct sites during in vitro aging of human growth hormone.
    J Biol Chem. 1989 Aug 25;264(24):14262-71 PMID: 2760065
  30. Identification of an isoaspartyl linkage formed upon deamidation of bovine calbindin D9k and structural characterization by 2D 1H NMR.
    Biochemistry. 1989 Oct 17;28(21):8646-53 PMID: 2605213
  31. Reduction of biological activity of murine recombinant interleukin-1 beta by selective deamidation at asparagine-149.
    FEBS Lett. 1991 Jan 14;278(1):98-102 PMID: 1993481
  32. Deamidation of soluble CD4 at asparagine-52 results in reduced binding capacity for the HIV-1 envelope glycoprotein gp120.
    Biochemistry. 1991 Apr 23;30(16):3916-22 PMID: 2018763
  33. Hemoglobin Redondo [beta 92(F8) His----Asn]: an unstable hemoglobin variant associated with heme loss which occurs in two forms.
    Am J Hematol. 1991 Nov;38(3):194-200 PMID: 1951318
  34. A potential allosteric subsite generated by domain swapping in bovine seminal ribonuclease.
    J Mol Biol. 1999 Oct 29;293(3):569-77 PMID: 10543951
  35. Effect of the three-dimensional structure on the deamidation reaction of ribonuclease A.
    J Pept Res. 1999 Nov;54(5):377-82 PMID: 10563503
  36. The effects of alpha-helix on the stability of Asn residues: deamidation rates in peptides of varying helicity.
    Protein Sci. 1999 Nov;8(11):2519-23 PMID: 10595558
  37. Terminal marking of triosephosphate isomerase: consequences of deamidation.
    Arch Biochem Biophys. 1995 Oct 1;322(2):361-8 PMID: 7574709
  38. Crystal structure of Ustilago sphaerogena ribonuclease U2 at 1.8 A resolution.
    Biochemistry. 1995 Nov 28;34(47):15583-91 PMID: 7492561
  39. Crystal structures of factor Xa specific inhibitors in complex with trypsin: structural grounds for inhibition of factor Xa and selectivity against thrombin.
    FEBS Lett. 1995 Nov 13;375(1-2):103-7 PMID: 7498454
  40. X-ray crystal structure of human acidic fibroblast growth factor.
    Biochemistry. 1996 Feb 20;35(7):2086-94 PMID: 8652550
  41. Hemoglobin S/hemoglobin Osler: a case with 3 beta globin chains. DNA sequence (AAT) proves that Hb Osler is beta 145 Tyr-->Asn.
    Am J Hematol. 1996 Aug;52(4):305-9 PMID: 8701949
  42. Kinetic and structural analysis of mutant CD4 receptors that are defective in HIV gp120 binding.
    Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15030-5 PMID: 8986758
  43. Product binding and role of the C-terminal region in class I D-fructose 1,6-bisphosphate aldolase.
    Nat Struct Biol. 1997 Jan;4(1):36-9 PMID: 8989320
  44. The crystal structure of the liver fatty acid-binding protein. A complex with two bound oleates.
    J Biol Chem. 1997 Mar 14;272(11):7140-50 PMID: 9054409
  45. Crystal structures of ribonuclease A complexes with 5'-diphosphoadenosine 3'-phosphate and 5'-diphosphoadenosine 2'-phosphate at 1.7 A resolution.
    Biochemistry. 1997 May 6;36(18):5578-88 PMID: 9154942
  46. The structures of deoxy human haemoglobin and the mutant Hb Tyralpha42His at 120 K.
    Acta Crystallogr D Biol Crystallogr. 2000 Jul;56(Pt 7):805-11 PMID: 10930827
  47. Molecular clocks.
    Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):944-9 PMID: 11158575
  48. A refined solution structure of hen lysozyme determined using residual dipolar coupling data.
    Protein Sci. 2001 Apr;10(4):677-88 PMID: 11274458
  49. On the heterogeneity of beef heart cytochrome c. 3. A kinetic study of the non-enzymic deamidation of the main subfractions (Cy I-Cy 3).
    Acta Chem Scand. 1966;20(6):1487-96 PMID: 5966864
  50. Multiple forms of cytochrome c in the rat. Precursor-product relationship between the main component Cy I and the minor components Cy II and Cy 3 in vivo.
    J Biol Chem. 1968 Apr 10;243(7):1623-9 PMID: 5647275
  51. Controlled deamidation of peptides and proteins: an experimental hazard and a possible biological timer.
    Proc Natl Acad Sci U S A. 1970 Jul;66(3):753-7 PMID: 5269237
  52. The specific nonenzymatic cleavage of bovine ribonuclease with hydroxylamine.
    J Biol Chem. 1970 Sep 25;245(18):4854-6 PMID: 5466069
  53. Kinetic study of the deamidation of growth hormone and prolactin.
    Biochim Biophys Acta. 1970 Sep 29;214(3):498-508 PMID: 5534305
  54. Deamidation in vivo of an asparagine residue of rabbit muscle aldolase.
    Proc Natl Acad Sci U S A. 1972 Jul;69(7):1816-9 PMID: 4505659
  55. Hemoglobin J Singapore: alpha 78 Asn--Asp; alpha 79 Ala--Gly.
    Biochim Biophys Acta. 1972 Oct 31;278(3):482-90 PMID: 5085670
  56. Rates of nonenzymatic deamidation of glutaminyl and asparaginyl residues in pentapeptides.
    J Am Chem Soc. 1973 Nov 28;95(24):8156-9 PMID: 4762548
  57. Primary sequence dependence of the deamidation of rabbit muscle aldolase.
    Science. 1974 Jan 11;183(4120):85 PMID: 4808790
  58. Evolution and the distribution of glutaminyl and asparaginyl residues in proteins.
    Proc Natl Acad Sci U S A. 1974 Mar;71(3):885-8 PMID: 4522799
  59. Deamidation of glutaminyl residues: dependence on pH, temperature, and ionic strength.
    Anal Biochem. 1974 May;59(1):319-22 PMID: 4407737
  60. Sequence dependent deamidation rates for model peptides of cytochrome C.
    Int J Pept Protein Res. 1974;6(1):31-5 PMID: 4369166
  61. Techniques of orthomolecular diagnosis.
    Clin Chem. 1974 Aug;20(8):961-5 PMID: 4854609
  62. Deamidation of glutaminyl and asparaginyl residues in peptides and proteins.
    Curr Top Cell Regul. 1974;8(0):247-95 PMID: 4371091
  63. Sequence dependent deamidation rates for model peptides of histone IV.
    Int J Pept Protein Res. 1974;6(5):279-82 PMID: 4430556
  64. Solution structure of murine epidermal growth factor determined by NMR spectroscopy and refined by energy minimization with restraints.
    Biochemistry. 1992 Jan 14;31(1):236-49 PMID: 1731873
  65. Structure of the EF corner favors deamidation of asparaginyl residues in hemoglobin: the example of Hb La Roche-sur-Yon [beta 81 (EF5) Leu----His].
    Biochim Biophys Acta. 1992 Feb 14;1138(2):127-32 PMID: 1540659
  66. Proline cis-trans isomers in calbindin D9k observed by X-ray crystallography.
    J Mol Biol. 1992 Feb 5;223(3):601-6 PMID: 1542107
  67. The structure of murine interleukin-1 beta at 2.8 A resolution.
    J Struct Biol. 1991 Oct;107(2):189-95 PMID: 1807351
  68. Analysis of human pituitary growth hormone and its charge variants by fast-atom bombardment mass spectrometry.
    Rapid Commun Mass Spectrom. 1991 Dec;5(12):579-81 PMID: 1811793
  69. Importance of asparagine-61 and asparagine-109 to the angiogenic activity of human angiogenin.
    Biochemistry. 1992 Sep 1;31(34):8022-9 PMID: 1380830
  70. Deamidation at asparagine-88 in recombinant human interleukin 2.
    Chem Pharm Bull (Tokyo). 1992 Apr;40(4):976-80 PMID: 1525954
  71. Chemical stability of insulin. 1. Hydrolytic degradation during storage of pharmaceutical preparations.
    Pharm Res. 1992 Jun;9(6):715-26 PMID: 1409351
  72. Structural and functional properties of hen egg-white lysozyme deamidated by protein engineering.
    Biosci Biotechnol Biochem. 1992 Sep;56(9):1424-8 PMID: 1368949
  73. Phosphotransferase and substrate binding mechanism of the cAMP-dependent protein kinase catalytic subunit from porcine heart as deduced from the 2.0 A structure of the complex with Mn2+ adenylyl imidodiphosphate and inhibitor peptide PKI(5-24).
    EMBO J. 1993 Mar;12(3):849-59 PMID: 8384554
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
2001-04-10
Pages
4367-72
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC31841
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com