1y79
From Proteopedia
(New page: 200px<br /><applet load="1y79" size="450" color="white" frame="true" align="right" spinBox="true" caption="1y79, resolution 2.00Å" /> '''Crystal Structure of...) |
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| - | [[Image:1y79.gif|left|200px]]<br /><applet load="1y79" size=" | + | [[Image:1y79.gif|left|200px]]<br /><applet load="1y79" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1y79, resolution 2.00Å" /> | caption="1y79, resolution 2.00Å" /> | ||
'''Crystal Structure of the E.coli Dipeptidyl Carboxypeptidase Dcp in Complex with a Peptidic Inhibitor'''<br /> | '''Crystal Structure of the E.coli Dipeptidyl Carboxypeptidase Dcp in Complex with a Peptidic Inhibitor'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Dcp from Escherichia coli is a 680 residue cytoplasmic peptidase, which | + | 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== | ==About this Structure== | ||
| - | 1Y79 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with ZN, LYS and GLY as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Peptidyl-dipeptidase_Dcp Peptidyl-dipeptidase Dcp], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.15.5 3.4.15.5] Full crystallographic information is available from [http:// | + | 1Y79 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=LYS:'>LYS</scene> and <scene name='pdbligand=GLY:'>GLY</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Peptidyl-dipeptidase_Dcp Peptidyl-dipeptidase Dcp], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.15.5 3.4.15.5] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y79 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: hinge bending; peptidyl dipeptidase; carboxypeptidase; dcp; neurolysin; ace]] | [[Category: hinge bending; peptidyl dipeptidase; carboxypeptidase; dcp; neurolysin; ace]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:02:24 2008'' |
Revision as of 14:02, 21 February 2008
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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 , and 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
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