1erq

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:1erq.jpg|left|200px]]
+
{{Seed}}
 +
[[Image:1erq.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_1erq| PDB=1erq | SCENE= }}
{{STRUCTURE_1erq| PDB=1erq | SCENE= }}
-
'''X-RAY CRYSTAL STRUCTURE OF TEM-1 BETA LACTAMASE IN COMPLEX WITH A DESIGNED BORONIC ACID INHIBITOR (1R)-1-ACETAMIDO-2-(3-CARBOXY-2-HYDROXYPHENYL)ETHYL BORONIC ACID'''
+
===X-RAY CRYSTAL STRUCTURE OF TEM-1 BETA LACTAMASE IN COMPLEX WITH A DESIGNED BORONIC ACID INHIBITOR (1R)-1-ACETAMIDO-2-(3-CARBOXY-2-HYDROXYPHENYL)ETHYL BORONIC ACID===
-
==Overview==
+
<!--
-
Transition state analogue boronic acid inhibitors mimicking the structures and interactions of good penicillin substrates for the TEM-1 beta-lactamase of Escherchia coli were designed using graphic analyses based on the enzyme's 1.7 A crystallographic structure. The synthesis of two of these transition state analogues, (1R)-1-phenylacetamido-2-(3-carboxyphenyl)ethylboronic acid (1) and (1R)-1-acetamido-2-(3-carboxy-2-hydroxyphenyl)ethylboronic acid (2), is reported. Kinetic measurements show that, as designed, compounds 1 and 2 are highly effective deacylation transition state analogue inhibitors of TEM-1 beta-lactamase, with inhibition constants of 5.9 and 13 nM, respectively. These values identify them as among the most potent competitive inhibitors yet reported for a beta-lactamase. The best inhibitor of the current series was (1R)-1-phenylacetamido-2-(3-carboxyphenyl)ethylboronic acid (1, K(I) = 5.9 nM), which resembles most closely the best known substrate of TEM-1, benzylpenicillin (penicillin G). The high-resolution crystallographic structures of these two inhibitors covalently bound to TEM-1 are also described. In addition to verifying the design features, these two structures show interesting and unanticipated changes in the active site area, including strong hydrogen bond formation, water displacement, and rearrangement of side chains. The structures provide new insights into the further design of this potent class of beta-lactamase inhibitors.
+
The line below this paragraph, {{ABSTRACT_PUBMED_10820001}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 10820001 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_10820001}}
==About this Structure==
==About this Structure==
Line 33: Line 37:
[[Category: Boronate inhibitor]]
[[Category: Boronate inhibitor]]
[[Category: Structure-based design]]
[[Category: Structure-based design]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 15:26:40 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 01:46:19 2008''

Revision as of 22:46, 30 June 2008

Image:1erq.png

Template:STRUCTURE 1erq

X-RAY CRYSTAL STRUCTURE OF TEM-1 BETA LACTAMASE IN COMPLEX WITH A DESIGNED BORONIC ACID INHIBITOR (1R)-1-ACETAMIDO-2-(3-CARBOXY-2-HYDROXYPHENYL)ETHYL BORONIC ACID

Template:ABSTRACT PUBMED 10820001

About this Structure

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

Reference

Structure-based design guides the improved efficacy of deacylation transition state analogue inhibitors of TEM-1 beta-Lactamase(,)., Ness S, Martin R, Kindler AM, Paetzel M, Gold M, Jensen SE, Jones JB, Strynadka NC, Biochemistry. 2000 May 9;39(18):5312-21. PMID:10820001

Page seeded by OCA on Tue Jul 1 01:46:19 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

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