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PDBsum entry 1klt
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Serine protease PDB id
1klt

 

 

 

 

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Contents
Protein chain
226 a.a. *
Ligands
PMS
Waters ×663
* Residue conservation analysis
PDB id:
1klt
Name: Serine protease
Title: Crystal structure of pmsf-treated human chymase at 1.9 angstroms resolution
Structure: Chymase. Chain: a. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: bacillus subtilis. Expression_system_taxid: 1423. Expression_system_variant: protease deficient
Resolution:
1.90Å     R-factor:   0.183     R-free:   0.255
Authors: M.E.Mcgrath
Key ref:
M.E.McGrath et al. (1997). Crystal structure of phenylmethanesulfonyl fluoride-treated human chymase at 1.9 A. Biochemistry, 36, 14318-14324. PubMed id: 9400368 DOI: 10.1021/bi971403n
Date:
16-Oct-97     Release date:   09-Dec-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P23946  (CMA1_HUMAN) -  Chymase from Homo sapiens
Seq:
Struc: 		247 a.a.
226 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.3.4.21.39  - chymase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Preferential cleavage: Phe-|-Xaa > Tyr-|-Xaa > Trp-|-Xaa > Leu-|-Xaa.

 

 
DOI no: 10.1021/bi971403n Biochemistry 36:14318-14324 (1997)
PubMed id: 9400368  
 
 
Crystal structure of phenylmethanesulfonyl fluoride-treated human chymase at 1.9 A.
M.E.McGrath, T.Mirzadegan, B.F.Schmidt.
 
  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.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20673209 E.V.Osipova, I.R.Chechetkin, Y.V.Gogolev, and N.B.Tarasova (2010).
Recombinant maize 9-lipoxygenase: expression, purification, and properties.
  Biochemistry (Mosc), 75, 861-865.  
20423454 M.K.Andersson, M.Thorpe, and L.Hellman (2010).
Arg143 and Lys192 of the human mast cell chymase mediate the preference for acidic amino acids in position P2' of substrates.
  FEBS J, 277, 2255-2267.  
19073880 M.K.Andersson, M.Enoksson, M.Gallwitz, and L.Hellman (2009).
The extended substrate specificity of the human mast cell chymase reveals a serine protease with well-defined substrate recognition profile.
  Int Immunol, 21, 95.  
18516248 G.H.Caughey (2006).
A Pulmonary Perspective on GASPIDs: Granule-Associated Serine Peptidases of Immune Defense.
  Curr Respir Med Rev, 2, 263-277.  
15741158 L.de Garavilla, M.N.Greco, N.Sukumar, Z.W.Chen, A.O.Pineda, F.S.Mathews, E.Di Cera, E.C.Giardino, G.I.Wells, B.J.Haertlein, J.A.Kauffman, T.W.Corcoran, C.K.Derian, A.J.Eckardt, B.P.Damiano, P.Andrade-Gordon, and B.E.Maryanoff (2005).
A novel, potent dual inhibitor of the leukocyte proteases cathepsin G and chymase: molecular mechanisms and anti-inflammatory activity in vivo.
  J Biol Chem, 280, 18001-18007.
PDB codes: 1t31 1t32
15123647 S.W.Ruggles, R.J.Fletterick, and C.S.Craik (2004).
Characterization of structural determinants of granzyme B reveals potent mediators of extended substrate specificity.
  J Biol Chem, 279, 30751-30759.  
14536074 M.A.Wouters, K.Liu, P.Riek, and A.Husain (2003).
A despecialization step underlying evolution of a family of serine proteases.
  Mol Cell, 12, 343-354.  
12815038 W.W.Raymond, S.W.Ruggles, C.S.Craik, and G.H.Caughey (2003).
Albumin is a substrate of human chymase. Prediction by combinatorial peptide screening and development of a selective inhibitor based on the albumin cleavage site.
  J Biol Chem, 278, 34517-34524.  
11973405 C.F.Santos, E.B.Oliveira, M.C.Salgado, and A.S.Greene (2002).
Molecular cloning and sequencing of the cDNA for rat mesenteric arterial bed elastase-2, an angiotensin II-forming enzyme.
  J Cardiovasc Pharmacol, 39, 628-635.  
12384499 C.Hink-Schauer, E.Estébanez-Perpiñá, E.Wilharm, P.Fuentes-Prior, W.Klinkert, W.Bode, and D.E.Jenne (2002).
The 2.2-A crystal structure of human pro-granzyme K reveals a rigid zymogen with unusual features.
  J Biol Chem, 277, 50923-50933.
PDB codes: 1mza 1mzd
11209755 E.Estébanez-Perpiña, P.Fuentes-Prior, D.Belorgey, M.Braun, R.Kiefersauer, K.Maskos, R.Huber, H.Rubin, and W.Bode (2000).
Crystal structure of the caspase activator human granzyme B, a proteinase highly specific for an Asp-P1 residue.
  Biol Chem, 381, 1203-1214.
PDB code: 1fq3
10102985 H.Czapinska, and J.Otlewski (1999).
Structural and energetic determinants of the S1-site specificity in serine proteases.
  Eur J Biochem, 260, 571-595.  
10318785 S.Réhault, M.Brillard-Bourdet, M.A.Juliano, L.Juliano, F.Gauthier, and T.Moreau (1999).
New, sensitive fluorogenic substrates for human cathepsin G based on the sequence of serpin-reactive site loops.
  J Biol Chem, 274, 13810-13817.  
10465545 W.C.Groutas, N.M.Schechter, S.He, H.Yu, P.Huang, and J.Tu (1999).
Human chymase inhibitors based on the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold.
  Bioorg Med Chem Lett, 9, 2199-2204.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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