1R42

Native Human Angiotensin Converting Enzyme-Related Carboxypeptidase (ACE2)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.287 
  • R-Value Work: 0.235 

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This is version 1.4 of the entry. See complete history


Literature

ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis.

Towler, P.Staker, B.Prasad, S.G.Menon, S.Tang, J.Parsons, T.Ryan, D.Fisher, M.Williams, D.Dales, N.A.Patane, M.A.Pantoliano, M.W.

(2004) J Biol Chem 279: 17996-18007

  • DOI: https://doi.org/10.1074/jbc.M311191200
  • Primary Citation of Related Structures:  
    1R42, 1R4L

  • PubMed Abstract: 

    The angiotensin-converting enzyme (ACE)-related carboxypeptidase, ACE2, is a type I integral membrane protein of 805 amino acids that contains one HEXXH + E zinc-binding consensus sequence. ACE2 has been implicated in the regulation of heart function and also as a functional receptor for the coronavirus that causes the severe acute respiratory syndrome (SARS). To gain further insights into this enzyme, the first crystal structures of the native and inhibitor-bound forms of the ACE2 extracellular domains were solved to 2.2- and 3.0-A resolution, respectively. Comparison of these structures revealed a large inhibitor-dependent hinge-bending movement of one catalytic subdomain relative to the other ( approximately 16 degrees ) that brings important residues into position for catalysis. The potent inhibitor MLN-4760 ((S,S)-2-[1-carboxy-2-[3-(3,5-dichlorobenzyl)-3H-imidazol4-yl]-ethylamino]-4-methylpentanoic acid) makes key binding interactions within the active site and offers insights regarding the action of residues involved in catalysis and substrate specificity. A few active site residue substitutions in ACE2 relative to ACE appear to eliminate the S(2)' substrate-binding subsite and account for the observed reactivity change from the peptidyl dipeptidase activity of ACE to the carboxypeptidase activity of ACE2.


  • Organizational Affiliation

    Drug Discovery and Protein Sciences, Millennium Pharmaceuticals, Incorporated, Cambridge, Massachusetts 02139, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
angiotensin I converting enzyme 2615Homo sapiensMutation(s): 0 
Gene Names: ACE2
UniProt & NIH Common Fund Data Resources
Find proteins for Q9BYF1 (Homo sapiens)
Explore Q9BYF1 
Go to UniProtKB:  Q9BYF1
PHAROS:  Q9BYF1
GTEx:  ENSG00000130234 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9BYF1
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
disordered segment of collectrin homology domain6Homo sapiensMutation(s): 0 
Gene Names: ACE2
Sequence Annotations
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  • Reference Sequence

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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
disordered segment of collectrin homology domain20Homo sapiensMutation(s): 0 
Gene Names: ACE2
Sequence Annotations
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  • Reference Sequence

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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
disordered segment of collectrin homology domain18Homo sapiensMutation(s): 0 
Gene Names: ACE2
Sequence Annotations
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  • Reference Sequence

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Entity ID: 5
MoleculeChains Sequence LengthOrganismDetailsImage
disordered segment of collectrin homology domain14Homo sapiensMutation(s): 0 
Gene Names: ACE2
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.287 
  • R-Value Work: 0.235 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 103.638α = 90
b = 89.478β = 109.15
c = 112.399γ = 90
Software Package:
Software NamePurpose
CNXrefinement
DENZOdata reduction
SCALEPACKdata scaling
MLPHAREphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-02-03
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.3: 2018-01-24
    Changes: Database references
  • Version 1.4: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations, Structure summary