1g2a

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:1g2a.gif|left|200px]]
+
{{Seed}}
 +
[[Image:1g2a.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_1g2a| PDB=1g2a | SCENE= }}
{{STRUCTURE_1g2a| PDB=1g2a | SCENE= }}
-
'''THE CRYSTAL STRUCTURE OF E.COLI PEPTIDE DEFORMYLASE COMPLEXED WITH ACTINONIN'''
+
===THE CRYSTAL STRUCTURE OF E.COLI PEPTIDE DEFORMYLASE COMPLEXED WITH ACTINONIN===
-
==Overview==
+
<!--
-
Peptide deformylase (PDF) is an essential bacterial metalloenzyme which deformylates the N-formylmethionine of newly synthesized polypeptides and as such represents a novel target for antibacterial chemotherapy. To identify novel PDF inhibitors, we screened a metalloenzyme inhibitor library and identified an N-formyl-hydroxylamine derivative, BB-3497, and a related natural hydroxamic acid antibiotic, actinonin, as potent and selective inhibitors of PDF. To elucidate the interactions that contribute to the binding affinity of these inhibitors, we determined the crystal structures of BB-3497 and actinonin bound to Escherichia coli PDF at resolutions of 2.1 and 1.75 A, respectively. In both complexes, the active-site metal atom was pentacoordinated by the side chains of Cys 90, His 132, and His 136 and the two oxygen atoms of N-formyl-hydroxylamine or hydroxamate. BB-3497 had activity against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis, and activity against some gram-negative bacteria. Time-kill analysis showed that the mode of action of BB-3497 was primarily bacteriostatic. The mechanism of resistance was via mutations within the formyltransferase gene, as previously described for actinonin. While actinonin and its derivatives have not been used clinically because of their poor pharmacokinetic properties, BB-3497 was shown to be orally bioavailable. A single oral dose of BB-3497 given 1 h after intraperitoneal injection of S. aureus Smith or methicillin-resistant S. aureus protected mice from infection with median effective doses of 8 and 14 mg/kg of body weight, respectively. These data validate PDF as a novel target for the design of a new generation of antibacterial agents.
+
The line below this paragraph, {{ABSTRACT_PUBMED_11158755}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 11158755 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_11158755}}
==About this Structure==
==About this Structure==
Line 39: Line 43:
[[Category: Inhibition]]
[[Category: Inhibition]]
[[Category: Polypeptide deformylase]]
[[Category: Polypeptide deformylase]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 17:02:39 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 04:18:03 2008''

Revision as of 01:18, 1 July 2008

Image:1g2a.png

Template:STRUCTURE 1g2a

THE CRYSTAL STRUCTURE OF E.COLI PEPTIDE DEFORMYLASE COMPLEXED WITH ACTINONIN

Template:ABSTRACT PUBMED 11158755

About this Structure

1G2A is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

Reference

Antibiotic activity and characterization of BB-3497, a novel peptide deformylase inhibitor., Clements JM, Beckett RP, Brown A, Catlin G, Lobell M, Palan S, Thomas W, Whittaker M, Wood S, Salama S, Baker PJ, Rodgers HF, Barynin V, Rice DW, Hunter MG, Antimicrob Agents Chemother. 2001 Feb;45(2):563-70. PMID:11158755

Page seeded by OCA on Tue Jul 1 04:18:03 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1g2a"
Personal tools