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| - | [[Image:2p8o.jpg|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_2p8o| PDB=2p8o | SCENE= }} | | {{STRUCTURE_2p8o| PDB=2p8o | SCENE= }} |
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| - | '''Crystal Structure of a Benzohydroxamic Acid/Vanadate complex bound to chymotrypsin A'''
| + | ===Crystal Structure of a Benzohydroxamic Acid/Vanadate complex bound to chymotrypsin A=== |
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| - | ==Overview==
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| - | Serine proteases, like serine beta-lactamases, are rapidly and covalently inhibited by suitably designed phosph(on)ates. The active sites of these enzymes must, therefore, be able to stabilize the pentacoordinated transition states of phosphyl transfer reactions as well as the tetrahedral transition states of acyl transfers. It follows that these enzymes should also be inhibited by molecules capable of generating inert pentacoordinated species. We (J.H.B. and R.F.P.) have previously shown that these enzymes are, in fact, rapidly and reversibly inhibited by 1:1 complexes of vanadate and hydroxamic acids. In this paper, we present the first crystal structure of an acyl transferase inhibited by vanadate. The complex of vanadate and benzohydroxamic acid is a competitive inhibitor of alpha-chymotrypsin with a KI value of 16 muM. In the structure, obtained at a resolution of 1.5 A, the protein is conformationally little different from the apoenzyme. The vanadium, in a distorted octahedral ligand field, is covalently bound to the active site serine oxygen group. One oxgen ligand, presumably anionic, is located in the oxyanion hole. Another is directed roughly in the direction of the acyl transfer leaving group, and a third in the direction of the S2 site. The hydroxamate is bound to vanadium through the hydroxyl oxygen and also, more weakly, through the carbonyl group, to form a five-membered chelate ring. The effect of this chelation is to place the phenyl group of the inhibitor into the important S1 specificity site. The hydroxamate oxygen is directed in line away from the Ser195 Ogamma, approximating the direction of departure of a leaving group in phosphyl transfer. The entire complex can be seen as a reasonable mimic of a phosphyl transfer transition state where the leaving group is extended into the S1 site.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_17469803}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 17469803 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_17469803}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Ringe, D.]] | | [[Category: Ringe, D.]] |
| | [[Category: Protein-inhibitor complex]] | | [[Category: Protein-inhibitor complex]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 12:36:59 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 18:58:35 2008'' |
Revision as of 15:58, 28 July 2008
Template:STRUCTURE 2p8o
Crystal Structure of a Benzohydroxamic Acid/Vanadate complex bound to chymotrypsin A
Template:ABSTRACT PUBMED 17469803
About this Structure
2P8O is a Protein complex structure of sequences from Bos taurus. Full crystallographic information is available from OCA.
Reference
Inhibition of chymotrypsin by a complex of ortho-vanadate and benzohydroxamic acid: structure of the inert complex and its mechanistic interpretation., Moulin A, Bell JH, Pratt RF, Ringe D, Biochemistry. 2007 May 22;46(20):5982-90. Epub 2007 May 1. PMID:17469803
Page seeded by OCA on Mon Jul 28 18:58:35 2008
