On the specificity of carboxypeptidase N, a comparative study.
The structure of the enzymatically active subunit of human plasma carboxypeptidase N was modeled based on the homology with bovine carboxypeptidase A. The active site of carboxypeptidase N is well conserved in comparison with carboxypeptidase A. From a comparison of energetically favorable binding sites for different atomic probe groups a hypothesis for the differences in substrate specificity between carboxypeptidases A and N was derived. Small synthetic peptide substrates were synthesized to confirm this hypothesis. This study shows that even with very low homology model building by homology can be employed to build models of sufficient quality to aid in drug design.
Hendriks
D
D
Department of Pharmaceutical Sciences, University of Antwerp, Belgium.
Vingron
M
M
Vriend
G
G
Wang
W
W
Nalis
D
D
Scharpé
S
S
D000595:Amino Acid Sequence; D000818:Animals; D043424:Carboxypeptidase B; D002268:Carboxypeptidases / Q000097:blood / Q000737:chemistry; D043422:Carboxypeptidases A; D002417:Cattle; D006801:Humans; D001121:Lysine Carboxypeptidase / Q000097:blood / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008970:Molecular Weight; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
D002268:Carboxypeptidases; D043422:Carboxypeptidases A; D043424:Carboxypeptidase B; D001121:Lysine Carboxypeptidase