1mxo

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:1mxo.jpg|left|200px]]<br /><applet load="1mxo" size="350" color="white" frame="true" align="right" spinBox="true"
+
[[Image:1mxo.jpg|left|200px]]
-
caption="1mxo, resolution 1.83&Aring;" />
+
 
-
'''AmpC beta-lactamase in complex with an m.carboxyphenylglycylboronic acid bearing the cephalothin R1 side chain'''<br />
+
{{Structure
 +
|PDB= 1mxo |SIZE=350|CAPTION= <scene name='initialview01'>1mxo</scene>, resolution 1.83&Aring;
 +
|SITE=
 +
|LIGAND= <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene> and <scene name='pdbligand=SM2:(1R)-1-(2-THIENYLACETYLAMINO)-1-(3-CARBOXYPHENYL)METHYLBORONIC ACID'>SM2</scene>
 +
|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]
 +
|GENE= ampc ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli])
 +
}}
 +
 
 +
'''AmpC beta-lactamase in complex with an m.carboxyphenylglycylboronic acid bearing the cephalothin R1 side chain'''
 +
 
==Overview==
==Overview==
Line 7: Line 16:
==About this Structure==
==About this Structure==
-
1MXO 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=SM2:'>SM2</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=1MXO OCA].
+
1MXO 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=1MXO OCA].
==Reference==
==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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12526668 12526668]
+
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]]
Line 28: Line 37:
[[Category: serine hydrolase]]
[[Category: serine hydrolase]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:00:07 2008''
+
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:49:34 2008''

Revision as of 10:49, 20 March 2008

Image:1mxo.jpg


PDB ID 1mxo

Drag the structure with the mouse to rotate
, resolution 1.83Å
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

1MXO 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

Page seeded by OCA on Thu Mar 20 12:49:34 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1mxo"
Personal tools