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PDBsum entry 1nn6
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protein ligands links
Hydrolase PDB id
1nn6

 

 

 

 

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Contents
Protein chain
222 a.a. *
Ligands
NAG-NAG
NAG
Waters ×153
* Residue conservation analysis
PDB id:
1nn6
Name: Hydrolase
Title: Human pro-chymase
Structure: Chymase. Chain: a. Synonym: mast cell protease i. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: human mast cell chymase gene. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9.
Resolution:
1.75Å     R-factor:   0.205     R-free:   0.245
Authors: K.K.Reiling,J.Krucinski,L.J.W.Miercke,W.W.Raymond,G.H.Caughey, R.M.Stroud
Key ref:
K.K.Reiling et al. (2003). Structure of human pro-chymase: a model for the activating transition of granule-associated proteases. Biochemistry, 42, 2616-2624. PubMed id: 12614156 DOI: 10.1021/bi020594d
Date:
12-Jan-03     Release date:   04-Mar-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P23946  (CMA1_HUMAN) -  Chymase from Homo sapiens
Seq:
Struc: 		247 a.a.
222 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 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/bi020594d Biochemistry 42:2616-2624 (2003)
PubMed id: 12614156  
 
 
Structure of human pro-chymase: a model for the activating transition of granule-associated proteases.
K.K.Reiling, J.Krucinski, L.J.Miercke, W.W.Raymond, G.H.Caughey, R.M.Stroud.
 
  ABSTRACT  
 
Human chymase is a protease involved in physiological processes ranging from inflammation to hypertension. As are all proteases of the trypsin fold, chymase is synthesized as an inactive "zymogen" with an N-terminal pro region that prevents the transition of the zymogen to an activated conformation. The 1.8 A structure of pro-chymase, reported here, is the first zymogen with a dipeptide pro region (glycine-glutamate) to be characterized at atomic resolution. Three segments of the pro-chymase structure differ from that of the activated enzyme: the N-terminus (Gly14-Gly19), the autolysis loop (Gly142-Thr154), and the 180s loop (Pro185A-Asp194). The four N-terminal residues (Gly14-Glu15-Ile16-Ile17) are disordered. The autolysis loop occupies a position up to 10 A closer to the active site than is seen in the activated enzyme, thereby forming a hydrogen bond with the catalytic residue Ser195 and occluding the S1' binding pocket. Nevertheless, the catalytic triad (Asp102-His57-Ser195) is arrayed in a geometry close to that seen in activated chymase (all atom rmsd of 0.52 A). The 180s loop of pro-chymase is, on average, 4 A removed from its conformation in the activated enzyme. This conformation disconnects the oxyanion hole (the amides of Gly193 and Ser195) from the active site and positions only approximately 35% of the S1-S3 binding pockets in the active conformation. The backbone of residue Asp194 is rotated 180 degrees when compared to its conformation in the activated enzyme, allowing a hydrogen bond between the main-chain amide of residue Trp141 and the carboxylate of Asp194. The side chains of residues Phe191 and Lys192 of pro-chymase fill the Ile16 binding pocket and the base of the S1 binding pocket, respectively. The zymogen positioning of both the 180s and autolysis loops are synergistic structural elements that appear to prevent premature proteolysis by chymase and, quite possibly, by other dipeptide zymogens.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20180651 A.A.Stoop, R.V.Joshi, C.T.Eggers, and C.S.Craik (2010).
Analysis of an engineered plasma kallikrein inhibitor and its effect on contact activation.
  Biol Chem, 391, 425-433.  
20809655 A.D.Vogt, A.Bah, and E.Di Cera (2010).
Evidence of the E*-E equilibrium from rapid kinetics of Na+ binding to activated protein C and factor Xa.
  J Phys Chem B, 114, 16125-16130.  
20974933 Z.Chen, L.A.Pelc, and E.Di Cera (2010).
Crystal structure of prethrombin-1.
  Proc Natl Acad Sci U S A, 107, 19278-19283.
PDB code: 3nxp
19473969 A.Bah, C.J.Carrell, Z.Chen, P.S.Gandhi, and E.Di Cera (2009).
Stabilization of the E* form turns thrombin into an anticoagulant.
  J Biol Chem, 284, 20034-20040.
PDB code: 3gic
19180666 E.Di Cera (2009).
Serine proteases.
  IUBMB Life, 61, 510-515.  
17102904 R.Sharma, V.Prasad, E.T.McCarthy, V.J.Savin, K.N.Dileepan, D.J.Stechschulte, E.Lianos, T.Wiegmann, and M.Sharma (2007).
Chymase increases glomerular albumin permeability via protease-activated receptor-2.
  Mol Cell Biochem, 297, 161-169.  
16788331 C.Bacani, and W.H.Frishman (2006).
Chymase: a new pharmacologic target in cardiovascular disease.
  Cardiol Rev, 14, 187-193.  
18516248 G.H.Caughey (2006).
A Pulmonary Perspective on GASPIDs: Granule-Associated Serine Peptidases of Immune Defense.
  Curr Respir Med Rev, 2, 263-277.  
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.  
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 code is shown on the right.

 

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