1PJP

THE 2.2 A CRYSTAL STRUCTURE OF HUMAN CHYMASE IN COMPLEX WITH SUCCINYL-ALA-ALA-PRO-PHE-CHLOROMETHYLKETONE


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.237 
  • R-Value Work: 0.184 
  • R-Value Observed: 0.184 

wwPDB Validation   3D Report Full Report


This is version 1.6 of the entry. See complete history


Literature

The 2.2 A crystal structure of human chymase in complex with succinyl-Ala-Ala-Pro-Phe-chloromethylketone: structural explanation for its dipeptidyl carboxypeptidase specificity.

Pereira, P.J.Wang, Z.M.Rubin, H.Huber, R.Bode, W.Schechter, N.M.Strobl, S.

(1999) J Mol Biol 286: 163-173

  • DOI: https://doi.org/10.1006/jmbi.1998.2462
  • Primary Citation of Related Structures:  
    1PJP

  • PubMed Abstract: 

    Human chymase (HC) is a chymotrypsin-like serine proteinase expressed by mast cells. The 2.2 A crystal structure of HC complexed to the peptidyl inhibitor, succinyl-Ala-Ala-Pro-Phe-chloromethylketone (CMK), was solved and refined to a crystallographic R-factor of 18.4 %. The HC structure exhibits the typical folding pattern of a chymotrypsin-like serine proteinase, and shows particularly similarity to rat chymase 2 (rat mast cell proteinase II) and human cathepsin G. The peptidyl-CMK inhibitor is covalently bound to the active-site residues Ser195 and His57; the peptidyl moiety juxtaposes the S1 entrance frame segment 214-217 by forming a short antiparallel beta-sheet. HC is a highly efficient angiotensin-converting enzyme. Modeling of the chymase-angiotensin I interaction guided by the geometry of the bound chloromethylketone inhibitor indicates that the extended substrate binding site contains features that may generate the dipeptidyl carboxypeptidase-like activity needed for efficient cleavage and activation of the hormone. The C-terminal carboxylate group of angiotensin I docked into the active-site cleft, with the last two residues extending beyond the active site, is perfectly localized to make a favorable hydrogen bond and salt bridge with the amide nitrogen of the Lys40-Phe41 peptide bond and with the epsilon-ammonium group of the Lys40 side-chain. This amide positioning is unique to the chymase-related proteinases, and only chymases from primates possess a Lys residue at position 40. Thus, the structure conveniently explains the preferred conversion of angiotensin I to angiotensin II by human chymase.


  • Organizational Affiliation

    Abteilung für Strukturforschung, Max-Planck-Institut für Biochemie, Am Klopferspitz 18a, Martinsried, D-82152, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CHYMASE226Homo sapiensMutation(s): 3 
EC: 3.4.21.39
UniProt & NIH Common Fund Data Resources
Find proteins for P23946 (Homo sapiens)
Explore P23946 
Go to UniProtKB:  P23946
PHAROS:  P23946
GTEx:  ENSG00000092009 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP23946
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
SUCCINYL-ALA-ALA-PRO-PHE-CHLOROMETHYLKETONE INHIBITORB [auth I]6N/AMutation(s): 0 
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAG
Query on NAG

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
E [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
HPH
Query on HPH
B [auth I]PEPTIDE-LIKEC9 H13 N O2PHE
Biologically Interesting Molecules (External Reference) 1 Unique
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.237 
  • R-Value Work: 0.184 
  • R-Value Observed: 0.184 
  • Space Group: P 43
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 74.37α = 90
b = 74.37β = 90
c = 50.09γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing
X-PLORrefinement

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1999-03-02
    Type: Initial release
  • Version 1.1: 2007-10-16
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Atomic model, Database references, Derived calculations, Non-polymer description, Structure summary, Version format compliance
  • Version 1.3: 2012-12-12
    Changes: Other
  • Version 1.4: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Data collection, Derived calculations, Structure summary
  • Version 1.5: 2021-11-03
    Changes: Advisory, Database references, Structure summary
  • Version 1.6: 2023-08-16
    Changes: Data collection, Refinement description