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Crystal structure of phenylmethanesulfonyl fluoride-treated human chymase at 1.9 A.

McGrath ME, Mirzadegan T, Schmidt BF
Biochemistry 36 14318-24 (1997)
Cited: 30 times
EuropePMC logo PMID: 9400368

Abstract

The X-ray crystal structure of human chymase has been determined to 1.9 A resolution using molecular replacement methods. This first structure of human chymase is present as the Ser 195 ester of alpha-toluenesulfonic acid. The refined structure (Rcryst = 0.183) shows that the inhibitor phenyl moiety lies at the top of the major specificity pocket, S1, while the sulfur is covalently linked to Ser 195-O gamma. The sulfonyl oxygens interact with the oxyanion hole and with His 57-N delta 1. The presence of the inhibitor disturbs the usual gauche position of His 57 and forces it to the trans conformer. Though the primary binding pockets are similarly specific in chymase and chymotrypsin, examination of the extended substrate binding sites reveals the structural basis for chymase's greater discrimination in choosing substrates. The larger 30s loop and its proximity to the active site indicates that it contacts substrate residues C-terminal to the scissile bond. Modeling of substrate at the chymase active site suggests that binding energy may be gained by three main-chain hydrogen bonds provided by substrate residues P2' and P4' and that discriminating interactions with substrate side chains are also likely. The presence of Lys 40 in S1' of human chymase explains its preference for Asp/Glu at P1'. Moreover, the cationic nature of S1' provides a structural basis for human chymase's poor catalytic efficiency when angiotensin II is the substrate.

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Reviews citing this publication (1)

  1. Structural and energetic determinants of the S1-site specificity in serine proteases. Czapinska H, Otlewski J. Eur J Biochem 260 571-595 (1999)

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  2. A novel, potent dual inhibitor of the leukocyte proteases cathepsin G and chymase: molecular mechanisms and anti-inflammatory activity in vivo. de Garavilla L, Greco MN, Sukumar N, Chen ZW, Pineda AO, Mathews FS, Di Cera E, Giardino EC, Wells GI, Haertlein BJ, Kauffman JA, Corcoran TW, Derian CK, Eckardt AJ, Damiano BP, Andrade-Gordon P, Maryanoff BE. J Biol Chem 280 18001-18007 (2005)
  3. The 2.2-A crystal structure of human pro-granzyme K reveals a rigid zymogen with unusual features. Hink-Schauer C, Estébanez-Perpiñá E, Wilharm E, Fuentes-Prior P, Klinkert W, Bode W, Jenne DE. J Biol Chem 277 50923-50933 (2002)
  4. A despecialization step underlying evolution of a family of serine proteases. Wouters MA, Liu K, Riek P, Husain A. Mol Cell 12 343-354 (2003)
  5. Crystal structure of the caspase activator human granzyme B, a proteinase highly specific for an Asp-P1 residue. Estébanez-Perpiña E, Fuentes-Prior P, Belorgey D, Braun M, Kiefersauer R, Maskos K, Huber R, Rubin H, Bode W. Biol Chem 381 1203-1214 (2000)
  6. The extended substrate specificity of the human mast cell chymase reveals a serine protease with well-defined substrate recognition profile. Andersson MK, Enoksson M, Gallwitz M, Hellman L. Int Immunol 21 95-104 (2009)
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  13. Thermal aggregation of alpha-chymotrypsin: role of hydrophobic and electrostatic interactions. Rezaei-Ghaleh N, Ramshini H, Ebrahim-Habibi A, Moosavi-Movahedi AA, Nemat-Gorgani M. Biophys Chem 132 23-32 (2008)
  14. Identification of a stable chymase inhibitor using a pharmacophore-Based database search. Koide Y, Tatsui A, Hasegawa T, Murakami A, Satoh S, Yamada H, Kazayama S, Takahashi A. Bioorg Med Chem Lett 13 25-29 (2003)
  15. Experimental Arthritis Is Dependent on Mouse Mast Cell Protease-5. Stevens RL, McNeil HP, Wensing LA, Shin K, Wong GW, Hansbro PM, Krilis SA. J Biol Chem 292 5392-5404 (2017)
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  18. A Pulmonary Perspective on GASPIDs: Granule-Associated Serine Peptidases of Immune Defense. Caughey GH. Curr Respir Med Rev 2 263-277 (2006)
  19. Structure-activity relationship of benzo[b]thiophene-2-sulfonamide derivatives as novel human chymase inhibitors. Masaki H, Mizuno Y, Tatui A, Murakami A, Koide Y, Satoh S, Takahashi A. Bioorg Med Chem Lett 13 4085-4088 (2003)
  20. Discriminating between the activities of human cathepsin G and chymase using fluorogenic substrates. Korkmaz B, Jégot G, Lau LC, Thorpe M, Pitois E, Juliano L, Walls AF, Hellman L, Gauthier F. FEBS J 278 2635-2646 (2011)
  21. Inhibitory mechanism of daphnodorins for human chymase. Sakaguchi M, Yamamoto D, Takai S, Jin D, Taniguchi M, Baba K, Miyazaki M. Biochem Biophys Res Commun 283 831-836 (2001)
  22. Recombinant maize 9-lipoxygenase: expression, purification, and properties. Osipova EV, Chechetkin IR, Gogolev YV, Tarasova NB. Biochemistry (Mosc) 75 861-865 (2010)


Related citations provided by authors (1)

  1. Production of Crystallizable Human Chymase from a Bacillus Subtilis System. Mcgrath ME, Osawa AE, Barnes MG, Clark JM, Mortara KD, Schmidt BF FEBS Lett. 413 486- (1997)

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