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Hydrolase PDB id
1j38
Jmol
Contents
Protein chains
598 a.a. *
Metals
_ZN ×2
Waters ×4
* Residue conservation analysis
PDB id:
1j38
Name: Hydrolase
Title: Crystal structure of drosophila ance
Structure: Angiotensin converting enzyme. Chain: a, b. Synonym: ance. Engineered: yes
Source: Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Resolution:
2.60Å     R-factor:   0.246     R-free:   0.281
Authors: H.M.Kim,D.R.Shin,H.Lee,J.-O.Lee
Key ref:
H.M.Kim et al. (2003). Crystal structure of Drosophila angiotensin I-converting enzyme bound to captopril and lisinopril. FEBS Lett, 538, 65-70. PubMed id: 12633854 DOI: 10.1016/S0014-5793(03)00128-5
Date:
20-Jan-03     Release date:   20-Jul-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
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
* PDB and UniProt seqs differ at 6 residue positions (black crosses)

 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: Zinc
 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/S0014-5793(03)00128-5 FEBS Lett 538:65-70 (2003)
PubMed id: 12633854  
 
 
Crystal structure of Drosophila angiotensin I-converting enzyme bound to captopril and lisinopril.
H.M.Kim, D.R.Shin, O.J.Yoo, H.Lee, J.O.Lee.
 
  ABSTRACT  
 
Angiotensin I-converting enzymes (ACEs) are zinc metallopeptidases that cleave carboxy-terminal dipeptides from short peptide hormones. We have determined the crystal structures of AnCE, a Drosophila homolog of ACE, with and without bound inhibitors to 2.4 A resolution. AnCE contains a large internal channel encompassing the entire protein molecule. This substrate-binding channel is composed of two chambers, reminiscent of a peanut shell. The inhibitor and zinc-binding sites are located in the narrow bottleneck connecting the two chambers. The substrate and inhibitor specificity of AnCE appears to be determined by extensive hydrogen-bonding networks and ionic interactions in the active site channel. The catalytically important zinc ion is coordinated by the conserved Glu395 and histidine residues from a HExxH motif.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Schematic diagram of the Drosophila AnCE structure. The zinc ion and the bound inhibitor, captopril, are shown in green and red, respectively. 		Figure 4.
Fig. 4. Proposed reaction intermediates of AnCE (A) and thermolysin (B). His337 and His497 of AnCE are located close to Tyr507 and may have an effect on catalysis. The scissile peptide bonds are marked with curved red lines.
 
  The above figures are reprinted by permission from the Federation of European Biochemical Societies: FEBS Lett (2003, 538, 65-70) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
18816584 A.S.Pina, and A.C.Roque (2009).
Studies on the molecular recognition between bioactive peptides and angiotensin-converting enzyme.
  J Mol Recognit, 22, 162-168.  
19656189 J.Simunic, D.Soyez, and N.Kamech (2009).
Characterization of a membrane-bound angiotensin-converting enzyme isoform in crayfish testis and evidence for its release into the seminal fluid.
  FEBS J, 276, 4727-4738.  
18214952 R.Minai, Y.Matsuo, H.Onuki, and H.Hirota (2008).
Method for comparing the structures of protein ligand-binding sites and application for predicting protein-drug interactions.
  Proteins, 72, 367-381.  
17429823 B.M.McArdle, and R.J.Quinn (2007).
Identification of protein fold topology shared between different folds inhibited by natural products.
  Chembiochem, 8, 788-798.  
17042482 J.M.Watermeyer, B.T.Sewell, S.L.Schwager, R.Natesh, H.R.Corradi, K.R.Acharya, and E.D.Sturrock (2006).
Structure of testis ACE glycosylation mutants and evidence for conserved domain movement.
  Biochemistry, 45, 12654-12663.
PDB codes: 2iul 2iux
16606345 P.Redelinghuys, A.T.Nchinda, K.Chibale, and E.D.Sturrock (2006).
Novel ketomethylene inhibitors of angiotensin I-converting enzyme (ACE): inhibition and molecular modelling.
  Biol Chem, 387, 461-466.  
16895474 Z.L.Woodman, S.L.Schwager, P.Redelinghuys, A.J.Chubb, E.L.van der Merwe, M.R.Ehlers, and E.D.Sturrock (2006).
Homologous substitution of ACE C-domain regions with N-domain sequences: effect on processing, shedding, and catalytic properties.
  Biol Chem, 387, 1043-1051.  
15883972 A.G.Tzakos, and I.P.Gerothanassis (2005).
Domain-selective ligand-binding modes and atomic level pharmacophore refinement in angiotensin I converting enzyme (ACE) inhibitors.
  Chembiochem, 6, 1089-1103.  
16008552 J.L.Guy, R.M.Jackson, H.A.Jensen, N.M.Hooper, and A.J.Turner (2005).
Identification of critical active-site residues in angiotensin-converting enzyme-2 (ACE2) by site-directed mutagenesis.
  FEBS J, 272, 3512-3520.  
15508121 A.S.Galanis, G.A.Spyroulias, G.Pairas, E.Manessi-Zoupa, and P.Cordopatis (2004).
Solid-phase synthesis and conformational properties of angiotensin converting enzyme catalytic-site peptides: the basis for a structural study on the enzyme-substrate interaction.
  Biopolymers, 76, 512-526.  
14998993 K.Ray, C.S.Hines, J.Coll-Rodriguez, and D.W.Rodgers (2004).
Crystal structure of human thimet oligopeptidase provides insight into substrate recognition, regulation, and localization.
  J Biol Chem, 279, 20480-20489.
PDB code: 1s4b
14754895 P.Towler, B.Staker, S.G.Prasad, S.Menon, J.Tang, T.Parsons, D.Ryan, M.Fisher, D.Williams, N.A.Dales, M.A.Patane, and M.W.Pantoliano (2004).
ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis.
  J Biol Chem, 279, 17996-18007.
PDB codes: 1r42 1r4l
12767125 A.S.Galanis, G.A.Spyroulias, R.Pierattelli, A.Tzakos, A.Troganis, I.P.Gerothanassis, G.Pairas, E.Manessi-Zoupa, and P.Cordopatis (2003).
Zinc binding in peptide models of angiotensin-I converting enzyme active sites studied through 1H-NMR and chemical shift perturbation mapping.
  Biopolymers, 69, 244-252.  
12914653 J.F.Riordan (2003).
Angiotensin-I-converting enzyme and its relatives.
  Genome Biol, 4, 225.  
  12915047 K.Brew (2003).
Structure of human ACE gives new insights into inhibitor binding and design.
  Trends Pharmacol Sci, 24, 391-394.  
14668810 K.R.Acharya, E.D.Sturrock, J.F.Riordan, and M.R.Ehlers (2003).
Ace revisited: a new target for structure-based drug design.
  Nat Rev Drug Discov, 2, 891-902.  
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.