From Proteopedia
(Difference between revisions)
proteopedia linkproteopedia link
|
|
| Line 1: |
Line 1: |
| - | [[Image:1r9c.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:1r9c.png|left|200px]] |
| | | | |
| | <!-- | | <!-- |
| Line 9: |
Line 10: |
| | {{STRUCTURE_1r9c| PDB=1r9c | SCENE= }} | | {{STRUCTURE_1r9c| PDB=1r9c | SCENE= }} |
| | | | |
| - | '''Crystal Structure of Fosfomycin Resistance Protein FosX from Mesorhizobium Loti'''
| + | ===Crystal Structure of Fosfomycin Resistance Protein FosX from Mesorhizobium Loti=== |
| | | | |
| | | | |
| - | ==Overview==
| + | <!-- |
| - | Microbial resistance to the antibiotic fosfomycin [(1R,2S)-epoxypropylphosphonic acid, 1] is known to be mediated by thiol transferase enzymes FosA and FosB, which catalyze the addition of glutathione and l-cysteine to C1 of the oxirane, respectively. A probe of the microbial genome database reveals a related group of enzymes (FosX). The genes mlr3345 from Mesorhizobium loti and lmo1702 from Listeria monocytogenes were cloned and the proteins expressed. This heretofore unrecognized group of enzymes is shown to catalyze the Mn(II)-dependent addition of water to C1 of the oxirane. The ability of each enzyme to confer resistance in Escherichia coli is correlated with their catalytic efficiency, such that the M. loti protein confers low resistance while the Listeria enzyme confers very robust resistance. The crystal structure of the FosX from M. loti was solved at a resolution of 1.83 A. The structure reveals an active-site carboxylate (E44) located about 5 A from the expected position of the substrate that appears to be poised to participate in catalysis. Single turnover experiments in H218O and kinetic analysis of the E44G mutant of the FosX enzymes indicate that the carboxylate of E44 acts as a general base in the direct addition of water to 1. The FosX from M. loti also catalyzes the addition of glutathione to the antibiotic. The catalytic promiscuity and low efficiency of the M. loti protein suggest that it may be an intermediate in the evolution of clinically relevant fosfomycin resistance proteins such as the FosX from Listeria monocytogenese.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_14677948}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 14677948 is the PubMed ID number. |
| | + | --> |
| | + | {{ABSTRACT_PUBMED_14677948}} |
| | | | |
| | ==About this Structure== | | ==About this Structure== |
| Line 30: |
Line 34: |
| | [[Category: Fosfomycin resistance protein]] | | [[Category: Fosfomycin resistance protein]] |
| | [[Category: Mn binding]] | | [[Category: Mn binding]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 07:13:56 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 04:06:58 2008'' |
Revision as of 01:06, 28 July 2008
Template:STRUCTURE 1r9c
Crystal Structure of Fosfomycin Resistance Protein FosX from Mesorhizobium Loti
Template:ABSTRACT PUBMED 14677948
About this Structure
1R9C is a Single protein structure of sequence from Mesorhizobium loti. Full crystallographic information is available from OCA.
Reference
Mechanistic diversity of fosfomycin resistance in pathogenic microorganisms., Fillgrove KL, Pakhomova S, Newcomer ME, Armstrong RN, J Am Chem Soc. 2003 Dec 24;125(51):15730-1. PMID:14677948
Page seeded by OCA on Mon Jul 28 04:06:58 2008
