A model of the ACE2 structure and function as a SARS-CoV receptor

Biochem Biophys Res Commun. 2004 Jan 30;314(1):235-41. doi: 10.1016/j.bbrc.2003.12.081.

Abstract

The angiotensin-converting enzyme 2 (ACE2) is an important regulator of the renin-angiotensin system and was very recently identified as a functional receptor for the SARS virus. The ACE2 sequence is similar (sequence identities 43% and 35%, and similarities 61% and 55%, respectively) to those of the testis-specific form of ACE (tACE) and the Drosophila homolog of ACE (AnCE). The high level of sequence similarity allowed us to build a robust homology model of the ACE2 structure with a root-mean-square deviation from the aligned crystal structures of tACE and AnCE less than 0.5A. A prominent feature of the model is a deep channel on the top of the molecule that contains the catalytic site. Negatively charged ridges surrounding the channel may provide a possible binding site for the positively charged receptor-binding domain (RBD) of the S-glycoprotein, which we recently identified [Biochem. Biophys. Res. Commun. 312 (2003) 1159]. Several distinct patches of hydrophobic residues at the ACE2 surface were noted at close proximity to the charged ridges that could contribute to binding. These results suggest a possible binding region for the SARS-CoV S-glycoprotein on ACE2 and could help in the design of experiments to further elucidate the structure and function of ACE2.

MeSH terms

  • Amino Acid Sequence
  • Angiotensin-Converting Enzyme 2
  • Binding Sites
  • Carboxypeptidases / chemistry*
  • Computer Simulation
  • Enzyme Stability
  • Models, Chemical*
  • Models, Molecular*
  • Molecular Sequence Data
  • Peptidyl-Dipeptidase A
  • Protein Binding
  • Protein Conformation
  • Receptors, Virus / chemistry*
  • Sequence Alignment / methods*
  • Sequence Analysis, Protein / methods*
  • Severe acute respiratory syndrome-related coronavirus / chemistry*
  • Structure-Activity Relationship
  • Surface Properties
  • Viral Fusion Proteins / chemistry*

Substances

  • Receptors, Virus
  • Viral Fusion Proteins
  • Carboxypeptidases
  • Peptidyl-Dipeptidase A
  • Angiotensin-Converting Enzyme 2