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Two polymorphs of a covalent complex between papain and a diazomethylketone inhibitor.

Janowski R, Kozak M, Jankowska E, Grzonka Z, Jaskólski M
J Pept Res 64 141-50 (2004)
Cited: 18 times
EuropePMC logo PMID: 15357669

Abstract

The three-dimensional structure of two polymorphs of a ZLFG-CH2-papain covalent complex has been determined by X-ray crystallography. The structures indicate that: (i) the methylene carbon atom of the inhibitor is covalently bound to the Sgamma atom of Cys25 of papain; (ii) the hydrophobic S2 pocket formed by Pro68, Val133, Val157, and Asp158 is occupied by the inhibitor's phenylalanyl P2 side chain; (iii) extensive hydrogen bonding and hydrophobic interactions are responsible for the interaction of the inhibitor with the enzyme. Comparison with similar structures suggests that in covalent complexes preservation of main chain-main chain interactions between the enzyme and the inhibitor may have higher priority than the P-S interactions.

Reviews - 1khp mentioned but not cited (1)

  1. Mechanisms of Proteolytic Enzymes and Their Inhibition in QM/MM Studies. Elsässer B, Goettig P. Int J Mol Sci 22 3232 (2021)

Articles - 1khp mentioned but not cited (4)

  1. Transient dimers of allergens. Rouvinen J, Jänis J, Laukkanen ML, Jylhä S, Niemi M, Päivinen T, Mäkinen-Kiljunen S, Haahtela T, Söderlund H, Takkinen K. PLoS One 5 e9037 (2010)
  2. Reaction pathway and free energy profile for papain-catalyzed hydrolysis of N-acetyl-Phe-Gly 4-nitroanilide. Wei D, Huang X, Liu J, Tang M, Zhan CG. Biochemistry 52 5145-5154 (2013)
  3. High-resolution complex of papain with remnants of a cysteine protease inhibitor derived from Trypanosoma brucei. Alphey MS, Hunter WN. Acta Crystallogr Sect F Struct Biol Cryst Commun 62 504-508 (2006)
  4. Molecular basis of specificity and deamidation of eIF4A by Burkholderia Lethal Factor 1. Mobbs GW, Aziz AA, Dix SR, Blackburn GM, Sedelnikova SE, Minshull TC, Dickman MJ, Baker PJ, Nathan S, Raih MF, Rice DW. Commun Biol 5 272 (2022)


Reviews citing this publication (1)

  1. New drug design with covalent modifiers. Adeniyi AA, Muthusamy R, Soliman ME. Expert Opin Drug Discov 11 79-90 (2016)

Articles citing this publication (12)

  1. Manual classification strategies in the ECOD database. Cheng H, Liao Y, Schaeffer RD, Grishin NV. Proteins 83 1238-1251 (2015)
  2. Distinct Roles of Catalytic Cysteine and Histidine in the Protease and Ligase Mechanisms of Human Legumain As Revealed by DFT-Based QM/MM Simulations. Elsässer B, Zauner FB, Messner J, Soh WT, Dall E, Brandstetter H. ACS Catal 7 5585-5593 (2017)
  3. Crystal structure of the parasite inhibitor chagasin in complex with papain allows identification of structural requirements for broad reactivity and specificity determinants for target proteases. Redzynia I, Ljunggren A, Bujacz A, Abrahamson M, Jaskolski M, Bujacz G. FEBS J 276 793-806 (2009)
  4. A bioorganometallic approach for the electrochemical detection of proteins: a study on the interaction of ferrocene-peptide conjugates with papain in solution and on Au surfaces. Mahmoud KA, Kraatz HB. Chemistry 13 5885-5895 (2007)
  5. Modelling family 2 cystatins and their interaction with papain. Nandy SK, Bhuyan R, Seal A. J Biomol Struct Dyn 31 649-664 (2013)
  6. Discovery of covalent enzyme inhibitors using virtual docking of covalent fragments. Chowdhury SR, Kennedy S, Zhu K, Mishra R, Chuong P, Nguyen AU, Kathman SG, Statsyuk AV. Bioorg Med Chem Lett 29 36-39 (2019)
  7. The oxyanion hole of Pseudomonas fluorescens mannitol 2-dehydrogenase: a novel structural motif for electrostatic stabilization in alcohol dehydrogenase active sites. Klimacek M, Nidetzky B. Biochem J 425 455-463 (2010)
  8. 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)
  9. 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)
  10. Conserved water-mediated H-bonding dynamics of catalytic Asn 175 in plant thiol protease. Nandi TK, Bairagya HR, Mukhopadhyay BP, Sekar K, Sukul D, Bera AK. J Biosci 34 27-34 (2009)
  11. Computational study on substrate specificity of a novel cysteine protease 1 precursor from Zea mays. Liu H, Chen L, Li Q, Zheng M, Liu J. Int J Mol Sci 15 10459-10478 (2014)
  12. Synthesis and evaluation of chloromethyl sulfoxides as a new class of selective irreversible cysteine protease inhibitors. Brouwer AJ, Bunschoten A, Liskamp RM. Bioorg Med Chem 15 6985-6993 (2007)


Related citations provided by authors (5)

  1. Crystallization and preliminary crystallographic studies of a new crystal form of papain from Carica papaya.. Kozak M, Kozian E, Grzonka Z, Jaskolski M Acta Biochim. Pol. 44 601-605 (1997)
  2. Structural studies of cysteine proteases and their inhibitors. Grzonka Z, Jankowska E, Wieczerzak E, Kasprzykowski F, Lankiewicz L, Wiczk W, Drabik P, Ciarkowski J, Janowski R, Kozak M, Jaskolski M, Grubb A Acta Biochim. Pol. 48 1-20 (2001)
  3. Binding of chloromethyl ketone substrate analogues to crystalline papain.. Drenth J, Kalk KH, Swen HM Biochemistry 15 3731-3738 (1976)
  4. Structure of monoclinic papain at 1.60 Angstroms resolution.. Pickersgill RW, Harris GW, Garman E Acta Crystallogr., B 48 59-66 (1992)
  5. Binding modes of a new epoxysuccinyl-peptide inhibitor of cysteine proteases. Where and how do cysteine proteases express their selectivity?. Czaplewski C, Grzonka Z, Jaskolski M, Kasprzykowski F, Kozak M, Politowska E, Ciarkowski J Biochim. Biophys. Acta 1431 290-305 (1999)

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