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1my8

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[[Image:1my8.jpg|left|200px]]<br /><applet load="1my8" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1my8.jpg|left|200px]]
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caption="1my8, resolution 1.72&Aring;" />
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'''AmpC beta-lactamase in complex with an M.carboxyphenylglycylboronic acid bearing the cephalothin R1 side chain'''<br />
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{{Structure
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|PDB= 1my8 |SIZE=350|CAPTION= <scene name='initialview01'>1my8</scene>, resolution 1.72&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene> and <scene name='pdbligand=SM3:(1R)-1-(2-THIENYLACETYLAMINO)-1-PHENYLMETHYLBORONIC ACID'>SM3</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= ampc ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli])
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}}
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'''AmpC beta-lactamase in complex with an M.carboxyphenylglycylboronic acid bearing the cephalothin R1 side chain'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1MY8 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=PO4:'>PO4</scene> and <scene name='pdbligand=SM3:'>SM3</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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MY8 OCA].
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1MY8 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MY8 OCA].
==Reference==
==Reference==
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Nanomolar inhibitors of AmpC beta-lactamase., Morandi F, Caselli E, Morandi S, Focia PJ, Blazquez J, Shoichet BK, Prati F, J Am Chem Soc. 2003 Jan 22;125(3):685-95. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12526668 12526668]
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Nanomolar inhibitors of AmpC beta-lactamase., Morandi F, Caselli E, Morandi S, Focia PJ, Blazquez J, Shoichet BK, Prati F, J Am Chem Soc. 2003 Jan 22;125(3):685-95. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12526668 12526668]
[[Category: Beta-lactamase]]
[[Category: Beta-lactamase]]
[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
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[[Category: serine hydrolase]]
[[Category: serine hydrolase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:00:17 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:49:50 2008''

Revision as of 10:49, 20 March 2008

Image:1my8.jpg


PDB ID 1my8

Drag the structure with the mouse to rotate
, resolution 1.72Å
Ligands: and
Gene: ampc (Escherichia coli)
Activity: Beta-lactamase, with EC number 3.5.2.6
Coordinates: save as pdb, mmCIF, xml



AmpC beta-lactamase in complex with an M.carboxyphenylglycylboronic acid bearing the cephalothin R1 side chain


Overview

beta-lactamases are the most widespread resistance mechanism to beta-lactam antibiotics, such as the penicillins and the cephalosporins. In an effort to combat these enzymes, a combination of stereoselective organic synthesis, enzymology, microbiology, and X-ray crystallography was used to design and evaluate new carboxyphenyl-glycylboronic acid transition-state analogue inhibitors of the class C beta-lactamase AmpC. The new compounds improve inhibition by over 2 orders of magnitude compared to analogous glycylboronic acids, with K(i) values as low as 1 nM. On the basis of the differential binding of different analogues, the introduced carboxylate alone contributes about 2.1 kcal/mol in affinity. This carboxylate corresponds to the ubiquitous C3(4)' carboxylate of beta-lactams, and this energy represents the first thermodynamic measurement of the importance of this group in molecular recognition by class C beta-lactamases. The structures of AmpC in complex with two of these inhibitors were determined by X-ray crystallography at 1.72 and 1.83 A resolution. These structures suggest a structural basis for the high affinity of the new compounds and provide templates for further design. The highest affinity inhibitor was 5 orders of magnitude more selective for AmpC than for characteristic serine proteases, such as chymotrypsin. This inhibitor reversed the resistance of clinical pathogens to the third generation cephalosporin ceftazidime; it may serve as a lead compound for drug discovery to combat bacterial resistance to beta-lactam antibiotics.

About this Structure

1MY8 is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

Reference

Nanomolar inhibitors of AmpC beta-lactamase., Morandi F, Caselli E, Morandi S, Focia PJ, Blazquez J, Shoichet BK, Prati F, J Am Chem Soc. 2003 Jan 22;125(3):685-95. PMID:12526668

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