2yz3

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(New page: 200px<br /><applet load="2yz3" size="350" color="white" frame="true" align="right" spinBox="true" caption="2yz3, resolution 2.30&Aring;" /> '''Crystallographic Inv...)
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[[Image:2yz3.jpg|left|200px]]<br /><applet load="2yz3" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:2yz3.jpg|left|200px]]
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caption="2yz3, resolution 2.30&Aring;" />
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'''Crystallographic Investigation of Inhibition Mode of the VIM-2 Metallo-beta-lactamase from Pseudomonas aeruginosa with Mercaptocarboxylate Inhibitor'''<br />
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{{Structure
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|PDB= 2yz3 |SIZE=350|CAPTION= <scene name='initialview01'>2yz3</scene>, resolution 2.30&Aring;
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|SITE= <scene name='pdbsite=AC1:Zn+Binding+Site+For+Residue+A+301'>AC1</scene>, <scene name='pdbsite=AC2:Zn+Binding+Site+For+Residue+A+302'>AC2</scene>, <scene name='pdbsite=AC3:Zn+Binding+Site+For+Residue+B+303'>AC3</scene>, <scene name='pdbsite=AC4:Zn+Binding+Site+For+Residue+B+304'>AC4</scene>, <scene name='pdbsite=AC5:So4+Binding+Site+For+Residue+B+501'>AC5</scene>, <scene name='pdbsite=AC6:So4+Binding+Site+For+Residue+A+502'>AC6</scene>, <scene name='pdbsite=AC7:So4+Binding+Site+For+Residue+A+503'>AC7</scene>, <scene name='pdbsite=AC8:So4+Binding+Site+For+Residue+B+504'>AC8</scene>, <scene name='pdbsite=AC9:M5p+Binding+Site+For+Residue+A+401'>AC9</scene> and <scene name='pdbsite=BC1:M5p+Binding+Site+For+Residue+B+402'>BC1</scene>
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|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=M5P:'>M5P</scene>
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|ACTIVITY= [http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6]
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|GENE= VIM-2, bla VIM-2, blaVIM-2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=303 Pseudomonas putida])
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}}
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'''Crystallographic Investigation of Inhibition Mode of the VIM-2 Metallo-beta-lactamase from Pseudomonas aeruginosa with Mercaptocarboxylate Inhibitor'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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2YZ3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_putida Pseudomonas putida] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=M5P:'>M5P</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] Known structural/functional Sites: <scene name='pdbsite=AC1:Zn+Binding+Site+For+Residue+A+301'>AC1</scene>, <scene name='pdbsite=AC2:Zn+Binding+Site+For+Residue+A+302'>AC2</scene>, <scene name='pdbsite=AC3:Zn+Binding+Site+For+Residue+B+303'>AC3</scene>, <scene name='pdbsite=AC4:Zn+Binding+Site+For+Residue+B+304'>AC4</scene>, <scene name='pdbsite=AC5:So4+Binding+Site+For+Residue+B+501'>AC5</scene>, <scene name='pdbsite=AC6:So4+Binding+Site+For+Residue+A+502'>AC6</scene>, <scene name='pdbsite=AC7:So4+Binding+Site+For+Residue+A+503'>AC7</scene>, <scene name='pdbsite=AC8:So4+Binding+Site+For+Residue+B+504'>AC8</scene>, <scene name='pdbsite=AC9:M5p+Binding+Site+For+Residue+A+401'>AC9</scene> and <scene name='pdbsite=BC1:M5p+Binding+Site+For+Residue+B+402'>BC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YZ3 OCA].
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2YZ3 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_putida Pseudomonas putida]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YZ3 OCA].
==Reference==
==Reference==
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Crystallographic investigation of the inhibition mode of a VIM-2 metallo-beta-lactamase from Pseudomonas aeruginosa by a mercaptocarboxylate inhibitor., Yamaguchi Y, Jin W, Matsunaga K, Ikemizu S, Yamagata Y, Wachino J, Shibata N, Arakawa Y, Kurosaki H, J Med Chem. 2007 Dec 27;50(26):6647-53. Epub 2007 Dec 6. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18052313 18052313]
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Crystallographic investigation of the inhibition mode of a VIM-2 metallo-beta-lactamase from Pseudomonas aeruginosa by a mercaptocarboxylate inhibitor., Yamaguchi Y, Jin W, Matsunaga K, Ikemizu S, Yamagata Y, Wachino J, Shibata N, Arakawa Y, Kurosaki H, J Med Chem. 2007 Dec 27;50(26):6647-53. Epub 2007 Dec 6. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18052313 18052313]
[[Category: Beta-lactamase]]
[[Category: Beta-lactamase]]
[[Category: Pseudomonas putida]]
[[Category: Pseudomonas putida]]
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[[Category: metallo-beta-lactamase]]
[[Category: metallo-beta-lactamase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Mar 14 09:37:20 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:50:28 2008''

Revision as of 16:50, 20 March 2008


PDB ID 2yz3

Drag the structure with the mouse to rotate
, resolution 2.30Å
Sites: , , , , , , , , and
Ligands: , and
Gene: VIM-2, bla VIM-2, blaVIM-2 (Pseudomonas putida)
Activity: Beta-lactamase, with EC number 3.5.2.6
Coordinates: save as pdb, mmCIF, xml



Crystallographic Investigation of Inhibition Mode of the VIM-2 Metallo-beta-lactamase from Pseudomonas aeruginosa with Mercaptocarboxylate Inhibitor


Overview

The VIM-2 metallo-beta-lactamase enzyme from Pseudomonas aeruginosa catalyzes the hydrolysis of most beta-lactam antibiotics including carbapenems, and there are currently no potent inhibitors of such enzymes. We found rac-2-omega-phenylpropyl-3-mercaptopropionic acid, phenylC3SH, to be a potent inhibitor of VIM-2. The structure of the VIM-2-phenylC3SH complex was determined by X-ray crystallography to 2.3 A. The structure revealed that the thiol group of phenylC3SH bridged to the two zinc(II) ions and the phenyl group interacted with Tyr67(47) on loop1 near the active site, by pi-pi stacking interactions. The methylene group interacted with Phe61(42) located at the bottom of loop1 through CH-pi interactions. Dynamic movements were observed in Arg228(185) and Asn233(190) on loop2, compared with the native structure (PDB code: 1KO3 ). These results suggest that the above-mentioned four residues play important roles in the binding and recognition of inhibitors or substrates and in stabilizing a loop in the VIM-2 enzyme.

About this Structure

2YZ3 is a Single protein structure of sequence from Pseudomonas putida. Full crystallographic information is available from OCA.

Reference

Crystallographic investigation of the inhibition mode of a VIM-2 metallo-beta-lactamase from Pseudomonas aeruginosa by a mercaptocarboxylate inhibitor., Yamaguchi Y, Jin W, Matsunaga K, Ikemizu S, Yamagata Y, Wachino J, Shibata N, Arakawa Y, Kurosaki H, J Med Chem. 2007 Dec 27;50(26):6647-53. Epub 2007 Dec 6. PMID:18052313

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