A model of the ACE2 structure and function as a SARS-CoV receptor.
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.
Prabakaran
Ponraj
P
Laboratory of Experimental and Computational Biology, CCR, NCI-Frederick, NIH, Frederick, MD 21702-1201, USA.
Xiao
Xiaodong
X
Dimitrov
Dimiter S
DS
D000595:Amino Acid Sequence; D000085962:Angiotensin-Converting Enzyme 2; D001665:Binding Sites; D002268:Carboxypeptidases / Q000737:chemistry*; D003198:Computer Simulation; D004795:Enzyme Stability; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D007703:Peptidyl-Dipeptidase A; D011485:Protein Binding; D011487:Protein Conformation; D011991:Receptors, Virus / Q000737:chemistry*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000737:chemistry*; D016415:Sequence Alignment / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000379:methods*; D013329:Structure-Activity Relationship; D013499:Surface Properties; D014760:Viral Fusion Proteins / Q000737:chemistry*
D011991:Receptors, Virus; D014760:Viral Fusion Proteins; D002268:Carboxypeptidases; D007703:Peptidyl-Dipeptidase A; D000085962:Angiotensin-Converting Enzyme 2