1y79
From Proteopedia
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Crystal Structure of the E.coli Dipeptidyl Carboxypeptidase Dcp in Complex with a Peptidic Inhibitor
Overview
Dcp from Escherichia coli is a 680 residue cytoplasmic peptidase, which, shows a strict dipeptidyl carboxypeptidase activity. Although Dcp had been, assigned to the angiotensin I-converting enzymes (ACE) due to blockage by, typical ACE inhibitors, it is currently grouped into the M3 family of mono, zinc peptidases, which also contains the endopeptidases neurolysin and, thimet oligopeptidase (TOP). We have cloned, expressed, purified, and, crystallized Dcp in the presence of an octapeptide "inhibitor", and have, determined its 2.0A crystal structure using MAD methods. The analysis, revealed that Dcp consists of two half shell-like subdomains, which, enclose an almost closed two-chamber cavity. In this cavity, two dipeptide, products presumably generated by Dcp cleavage of the octapeptide bind to, the thermolysin-like active site fixed to side-chains, which are provided, by both subdomains. In particular, an Arg side-chain backed by a Glu, residue, together with two Tyr phenolic groups provide a charged anchor, for fixing the C-terminal carboxylate group of the P2' residue of a bound, substrate, explaining the strict dipeptidyl carboxypeptidase specificity, of Dcp. Tetrapeptidic substrates are fixed only via their main-chain, functions from P2 to P2', suggesting a broad residue specificity for Dcp., Both subdomains exhibit very similar chain folds as the equivalent but, abducted subdomains of neurolysin and TOP. Therefore, this "product-bound", Dcp structure seems to represent the inhibitor/substrate-bound "closed", form of the M3 peptidases, generated from the free "open", substrate-accessible form by a hinge-bending mechanism. A similar, mechanism has recently been demonstrated experimentally for ACE2.
About this Structure
1Y79 is a Single protein structure of sequence from Escherichia coli with ZN, LYS and GLY as ligands. Active as Peptidyl-dipeptidase Dcp, with EC number 3.4.15.5 Full crystallographic information is available from OCA.
Reference
Crystal structure of the E. coli dipeptidyl carboxypeptidase Dcp: further indication of a ligand-dependent hinge movement mechanism., Comellas-Bigler M, Lang R, Bode W, Maskos K, J Mol Biol. 2005 May 27;349(1):99-112. Epub 2005 Mar 25. PMID:15876371
Page seeded by OCA on Wed Nov 21 06:36:58 2007
