1UZE

Complex of the anti-hypertensive drug enalaprilat and the human testicular angiotensin I-converting enzyme


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.82 Å
  • R-Value Free: 0.211 
  • R-Value Work: 0.188 
  • R-Value Observed: 0.188 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structural Details on the Binding of Antihypertensive Drugs Captopril and Enalaprilat to Human Testicular Angiotensin I-Converting Enzyme

Natesh, R.Schwager, S.L.U.Evans, H.R.Sturrock, E.D.Acharya, K.R.

(2004) Biochemistry 43: 8718

  • DOI: https://doi.org/10.1021/bi049480n
  • Primary Citation of Related Structures:  
    1UZE, 1UZF

  • PubMed Abstract: 

    Angiotensin converting enzyme (ACE) plays a critical role in the circulating or endocrine renin-angiotensin system (RAS) as well as the local regulation that exists in tissues such as the myocardium and skeletal muscle. Here we report the high-resolution crystal structures of testis ACE (tACE) in complex with the first successfully designed ACE inhibitor captopril and enalaprilat, the Phe-Ala-Pro analogue. We have compared these structures with the recently reported structure of a tACE-lisinopril complex [Natesh et al. (2003) Nature 421, 551-554]. The analyses reveal that all three inhibitors make direct interactions with the catalytic Zn(2+) ion at the active site of the enzyme: the thiol group of captopril and the carboxylate group of enalaprilat and lisinopril. Subtle differences are also observed at other regions of the binding pocket. These are compared with N-domain models and discussed with reference to published biochemical data. The chloride coordination geometries of the three structures are discussed and compared with other ACE analogues. It is anticipated that the molecular details provided by these structures will be used to improve the binding and/or the design of new, more potent domain-specific inhibitors of ACE that could serve as new generation antihypertensive drugs.


  • Organizational Affiliation

    Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, United Kingdom.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
ANGIOTENSIN CONVERTING ENZYME589Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P12821 (Homo sapiens)
Explore P12821 
Go to UniProtKB:  P12821
PHAROS:  P12821
GTEx:  ENSG00000159640 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP12821
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
EAL
Query on EAL

Download Ideal Coordinates CCD File 
F [auth A]1-((2S)-2-{[(1S)-1-CARBOXY-3-PHENYLPROPYL]AMINO}PROPANOYL)-L-PROLINE
C18 H24 N2 O5
LZFZMUMEGBBDTC-QEJZJMRPSA-N
GLY
Query on GLY

Download Ideal Coordinates CCD File 
B [auth A]GLYCINE
C2 H5 N O2
DHMQDGOQFOQNFH-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
C [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
D [auth A],
E [auth A]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Binding Affinity Annotations 
IDSourceBinding Affinity
EAL BindingDB:  1UZE IC50: min: 1.2, max: 3100 (nM) from 8 assay(s)
PDBBind:  1UZE IC50: 1.27 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.82 Å
  • R-Value Free: 0.211 
  • R-Value Work: 0.188 
  • R-Value Observed: 0.188 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 56.72α = 90
b = 85.35β = 90
c = 133.73γ = 90
Software Package:
Software NamePurpose
CNSrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-07-16
    Type: Initial release
  • Version 1.1: 2011-05-07
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance