PDBsum entry 2x92

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Hydrolase PDB id
Protein chain
598 a.a. *
NAG ×2
Waters ×401
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of ance-ramiprilat complex
Structure: Angiotensin converting enzyme. Chain: a. Fragment: residues 17-615. Synonym: dipeptidyl carboxypeptidase i, kininase ii. Engineered: yes
Source: Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Expressed in: pichia pastoris. Expression_system_taxid: 644223.
2.11Å     R-factor:   0.191     R-free:   0.218
Authors: M.Akif,D.Georgiadis,A.Mahajan,V.Dive,E.D.Sturrock,R.E.Isaac, K.R.Acharya
Key ref: M.Akif et al. (2010). High-resolution crystal structures of Drosophila melanogaster angiotensin-converting enzyme in complex with novel inhibitors and antihypertensive drugs. J Mol Biol, 400, 502-517. PubMed id: 20488190 DOI: 10.1016/j.jmb.2010.05.024
14-Mar-10     Release date:   02-Jun-10    
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Protein chain
Pfam   ArchSchema ?
Q10714  (ACE_DROME) -  Angiotensin-converting enzyme
615 a.a.
598 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - 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.jmb.2010.05.024 J Mol Biol 400:502-517 (2010)
PubMed id: 20488190  
High-resolution crystal structures of Drosophila melanogaster angiotensin-converting enzyme in complex with novel inhibitors and antihypertensive drugs.
M.Akif, D.Georgiadis, A.Mahajan, V.Dive, E.D.Sturrock, R.E.Isaac, K.R.Acharya.
Angiotensin-I converting enzyme (ACE), one of the central components of renin-angiotensin system, is a key therapeutic target for the treatment of hypertension and cardiovascular disorders. Human somatic ACE (sACE) has two homologous domains (N- and C-). The N- and C- domain catalytic sites have different activities toward various substrates. Moreover, some of the undesirable side effects of the currently available and widely used ACE inhibitors may arise from their targeting the wrong domain leading to defects in other signalling pathways. In addition, structural studies have shown that although both these domains have much in common at the inhibitor binding site, there are significant differences and these are greater at the peptide binding sites than regions distal to the active site. As a model system, we have used an ACE homolog from Drosophila melanogaster (AnCE, a single domain protein with ACE activity) to study ACE inhibitor binding. In an extensive study we present high resolution structures for native AnCE and in complex with six known anti-hypertensive drugs, a novel C- domain sACE specific inhibitor- lisW-S and two sACE domain-specific phosphinic peptidyl inhibitors- RXPA380 and RXP407 (i.e., nine structures). These structures show detailed binding features of the inhibitors and highlight subtle changes in the orientation of side-chains at different binding pockets in the active site in comparison with the active site of N- and C- domains of sACE. This study provides information about the structure-activity relationships which could be utilized for designing new inhibitors with improved domain selectivity for sACE.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20826823 C.S.Anthony, H.R.Corradi, S.L.Schwager, P.Redelinghuys, D.Georgiadis, V.Dive, K.R.Acharya, and E.D.Sturrock (2010).
The N domain of human angiotensin-I-converting enzyme: the role of N-glycosylation and the crystal structure in complex with an N domain-specific phosphinic inhibitor, RXP407.
  J Biol Chem, 285, 35685-35693.
PDB codes: 2oc2 3nxq
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