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PDBsum entry 2xhm

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protein ligands metals links
Hydrolase PDB id
2xhm
Jmol
Contents
Protein chain
598 a.a. *
Ligands
K26
EPE
NAG-NAG-BMA-BMA-
MAN
NAG ×2
MAN
Metals
_ZN
Waters ×490
* Residue conservation analysis
PDB id:
2xhm
Name: Hydrolase
Title: Crystal structure of ance-k26 complex
Structure: Angiotensin converting enzyme. Chain: a. Fragment: residues 17-614. Synonym: dipeptidyl carboxypeptidase i, kininase ii. Engineered: yes
Source: Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Expressed in: pichia pastoris. Expression_system_taxid: 644223.
Resolution:
1.96Å     R-factor:   0.195     R-free:   0.214
Authors: M.Akif,I.Ntai,E.D.Sturrock,R.E.Isaac,B.O.Bachmann, K.R.Achar
Key ref: M.Akif et al. (2010). Crystal structure of a phosphonotripeptide K-26 in complex with angiotensin converting enzyme homologue (AnCE) from Drosophila melanogaster. Biochem Biophys Res Commun, 398, 532-536. PubMed id: 20599761 DOI: 10.1016/j.bbrc.2010.06.113
Date:
18-Jun-10     Release date:   14-Jul-10    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q10714  (ACE_DROME) -  Angiotensin-converting enzyme
Seq:
Struc:
 
Seq:
Struc:
615 a.a.
598 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.4.15.1  - Peptidyl-dipeptidase A.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Release of a C-terminal dipeptide, oligopeptide-|-Xaa-Xbb, when Xaa is not Pro, and Xbb is neither Asp nor Glu. Converts angiotensin I to angiotensin II.
      Cofactor: Zn(2+)
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 
  Biological process     proteolysis   1 term 
  Biochemical function     metallopeptidase activity     2 terms  

 

 
DOI no: 10.1016/j.bbrc.2010.06.113 Biochem Biophys Res Commun 398:532-536 (2010)
PubMed id: 20599761  
 
 
Crystal structure of a phosphonotripeptide K-26 in complex with angiotensin converting enzyme homologue (AnCE) from Drosophila melanogaster.
M.Akif, I.Ntai, E.D.Sturrock, R.E.Isaac, B.O.Bachmann, K.R.Acharya.
 
  ABSTRACT  
 
Angiotensin-I converting enzyme (ACE, a zinc dependent dipeptidyl carboxypeptidase) is a major target of drugs due to its role in the modulation of blood pressure and cardiovascular disorders. Here we present a crystal structure of AnCE (an ACE homologue from Drosophila melanogaster with a single enzymatic domain) in complex with a natural product-phophonotripeptide, K-26 at 1.96 A resolution. The inhibitor binds exclusively in the S(1) and S(2) binding pockets of AnCE (coordinating the zinc ion) through ionic and hydrogen bond interactions. A detailed structural comparison of AnCE*K-26 complex with individual domains of human somatic ACE provides useful information for further exploration of ACE inhibitor pharmacophores involving phosphonic acids.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21130035 K.E.Bernstein, X.Z.Shen, R.A.Gonzalez-Villalobos, S.Billet, D.Okwan-Duodu, F.S.Ong, and S.Fuchs (2011).
Different in vivo functions of the two catalytic domains of angiotensin-converting enzyme (ACE).
  Curr Opin Pharmacol, 11, 105-111.  
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.