1gec Citations

Crystal structure of glycyl endopeptidase from Carica papaya: a cysteine endopeptidase of unusual substrate specificity.

Biochemistry 34 13190-5 (1995)
Cited: 25 times
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Glycyl endopeptidase is a cysteine endopeptidase of the papain family, characterized by specificity for cleavage C-terminal to glycyl residues only and by resistance to inhibition by members of the cystatin family of cysteine proteinase inhibitors. Glycyl endopeptidase has been crystallized from high salt with a substrate-like inhibitor covalently bound to the catalytic Cys 25. The structure has been solved by molecular replacement with the structure of papain and refined at 2.1 A to an R factor of 0.196 (Rfree = 0.258) with good geometry. The structure of the S1 substrate binding site of glycyl endopeptidase differs from that of papain by the substitution of glycines at residues 23 and 65 in papain, with glutamic acid and arginine, respectively, in glycyl endopeptidase. The side chains of these residues form a barrier across the binding pocket, effectively excluding substrate residues with large side chains from the S1 subsite. The constriction of this subsite in glycyl endopeptidase explains the unique specificity of this enzyme for cleavage after glycyl residues and is a major component of its resistance to inhibition by cystatins.

Articles - 1gec mentioned but not cited (2)

  1. Crystal structure of a deubiquitinating enzyme (human UCH-L3) at 1.8 A resolution. Johnston SC, Larsen CN, Cook WJ, Wilkinson KD, Hill CP. EMBO J. 16 3787-3796 (1997)
  2. Insight to structural subsite recognition in plant thiol protease-inhibitor complexes : understanding the basis of differential inhibition and the role of water. Bhattacharya S, Ghosh S, Chakraborty S, Bera AK, Mukhopadhayay BP, Dey I, Banerjee A. BMC Struct. Biol. 1 4 (2001)

Reviews citing this publication (5)

  1. Fractionation and purification of the enzymes stored in the latex of Carica papaya. Azarkan M, El Moussaoui A, van Wuytswinkel D, Dehon G, Looze Y. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 790 229-238 (2003)
  2. The lysosomal cysteine proteases. McGrath ME. Annu Rev Biophys Biomol Struct 28 181-204 (1999)
  3. Revised definition of substrate binding sites of papain-like cysteine proteases. Turk D, Guncar G, Podobnik M, Turk B. Biol. Chem. 379 137-147 (1998)
  4. The proteasome: a macromolecular assembly designed to confine proteolysis to a nanocompartment. Baumeister W, Cejka Z, Kania M, Seemüller E. Biol. Chem. 378 121-130 (1997)
  5. Proregion structure of members of the papain superfamily. Mode of inhibition of enzymatic activity. Cygler M, Mort JS. Biochimie 79 645-652 (1997)

Articles citing this publication (18)

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  2. The crystal structure of Pseudomonas avirulence protein AvrPphB: a papain-like fold with a distinct substrate-binding site. Zhu M, Shao F, Innes RW, Dixon JE, Xu Z. Proc. Natl. Acad. Sci. U.S.A. 101 302-307 (2004)
  3. MEROPS: the peptidase database. Rawlings ND, Barrett AJ. Nucleic Acids Res. 28 323-325 (2000)
  4. The prosequence of procaricain forms an alpha-helical domain that prevents access to the substrate-binding cleft. Groves MR, Taylor MA, Scott M, Cummings NJ, Pickersgill RW, Jenkins JA. Structure 4 1193-1203 (1996)
  5. Probing the specificity of cysteine proteinases at subsites remote from the active site: analysis of P4, P3, P2' and P3' variations in extended substrates. Portaro FC, Santos AB, Cezari MH, Juliano MA, Juliano L, Carmona E. Biochem. J. 347 Pt 1 123-129 (2000)
  6. Molecular basis of Colorado potato beetle adaptation to potato plant defence at the level of digestive cysteine proteinases. Gruden K, Kuipers AG, Guncar G, Slapar N, Strukelj B, Jongsma MA. Insect Biochem. Mol. Biol. 34 365-375 (2004)
  7. Structural and biochemical features distinguish the foot-and-mouth disease virus leader proteinase from other papain-like enzymes. Guarné A, Hampoelz B, Glaser W, Carpena X, Tormo J, Fita I, Skern T. J. Mol. Biol. 302 1227-1240 (2000)
  8. Critical role of amino acid 23 in mediating activity and specificity of vinckepain-2, a papain-family cysteine protease of rodent malaria parasites. Singh A, Shenai BR, Choe Y, Gut J, Sijwali PS, Craik CS, Rosenthal PJ. Biochem. J. 368 273-281 (2002)
  9. Structural insights into the protease-like antigen Plasmodium falciparum SERA5 and its noncanonical active-site serine. Hodder AN, Malby RL, Clarke OB, Fairlie WD, Colman PM, Crabb BS, Smith BJ. J. Mol. Biol. 392 154-165 (2009)
  10. Crystal structure of a caricain D158E mutant in complex with E-64. Katerelos NA, Taylor MA, Scott M, Goodenough PW, Pickersgill RW. FEBS Lett. 392 35-39 (1996)
  11. Carica papaya latex is a rich source of a class II chitinase. Azarkan M, Amrani A, Nijs M, Vandermeers A, Zerhouni S, Smolders N, Looze Y. Phytochemistry 46 1319-1325 (1997)
  12. Dissecting the active site of the collagenolytic cathepsin L3 protease of the invasive stage of Fasciola hepatica. Corvo I, O'Donoghue AJ, Pastro L, Pi-Denis N, Eroy-Reveles A, Roche L, McKerrow JH, Dalton JP, Craik CS, Caffrey CR, Tort JF. PLoS Negl Trop Dis 7 e2269 (2013)
  13. Foot-and-mouth disease virus leader proteinase: structural insights into the mechanism of intermolecular cleavage. Steinberger J, Grishkovskaya I, Cencic R, Juliano L, Juliano MA, Skern T. Virology 468-470 397-408 (2014)
  14. Conserved water-mediated H-bonding dynamics of catalytic His159 and Asp158: insight into a possible acid-base coupled mechanism in plant thiol protease. Nandi TK, Bairagya HR, Mukhopadhyay BP, Mallik P, Sukul D, Bera AK. J Mol Model 18 2633-2644 (2012)
  15. Binding modes of a new epoxysuccinyl-peptide inhibitor of cysteine proteases. Where and how do cysteine proteases express their selectivity? Czaplewski C, Grzonka Z, Jaskólski M, Kasprzykowski F, Kozak M, Politowska E, Ciarkowski J. Biochim. Biophys. Acta 1431 290-305 (1999)
  16. A novel form of ficin from Ficus carica latex: Purification and characterization. Baeyens-Volant D, Matagne A, El Mahyaoui R, Wattiez R, Azarkan M. Phytochemistry 117 154-167 (2015)
  17. X-ray crystal structure of CMS1MS2: a high proteolytic activity cysteine proteinase from Carica candamarcensis. Gomes MT, Teixeira RD, Lopes MT, Nagem RA, Salas CE. Amino Acids 43 2381-2391 (2012)
  18. An assessment of protein-ligand binding site polarizability. Nayeem A, Krystek S, Stouch T. Biopolymers 70 201-211 (2003)