Database accession: MF7000102
Name: FosX (Mesorhizobium Loti)
PDB ID: 1r9c
Experimental method: X-ray (1.83 Å)
Assembly: Homodimer
Source organism: Mesorhizobium japonicum
Primary publication of the structure:
Fillgrove KL, Pakhomova S, Newcomer ME, Armstrong RN
Mechanistic diversity of fosfomycin resistance in pathogenic microorganisms.
(2003) J. Am. Chem. Soc. 125: 15730-1
PMID: 14677948
Abstract:
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.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
metal ion binding metal ion binding
Biological process:
response to antibiotic response to antibiotic
Cellular component:
cytoplasm cytoplasm
Structural annotations of the participating protein chains.Entry contents: 2 distinct polypeptide molecules
Chains: A, B
Notes: All chains according to the most probable oligomerization state stored in PDBe were considered.
Number of unique protein segments: 1
Name: Fosfomycin resistance protein FosX
Source organism: Mesorhizobium japonicum
Length: 139 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMIEGLSHMTFIVRDLERMTRILEGVFDAREVYASDTEQFSLSREKFFLIGDIWVAIMQGEKLAERSYNHIAFKIDDADFDRYAERVGKLGLDMRPPRPRVEGEGRSIYFYDDDNHMFELHTGTLTERLARKAKGLEAAQ
UniProtKB AC: Q98GG1 (positions: 1-130)
Coverage: 93%
Name: Fosfomycin resistance protein FosX
Source organism: Mesorhizobium japonicum
Length: 139 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMIEGLSHMTFIVRDLERMTRILEGVFDAREVYASDTEQFSLSREKFFLIGDIWVAIMQGEKLAERSYNHIAFKIDDADFDRYAERVGKLGLDMRPPRPRVEGEGRSIYFYDDDNHMFELHTGTLTERLARKAKGLEAAQ
UniProtKB AC: Q98GG1 (positions: 1-129)
Coverage: 92%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily
Evidence level: Indirect evidence
Evidence coverage: The full structure participates in mutual synergistic folding.
Complex Evidence:
The VOC superfamily of metalloenzymes is characterized by a three-dimensional domain-swapped arrangement of tandem βαβββ-motifs (PMID:24447055). The original gene duplication event led to the βαβββ tandem structure, which appears to require dimerization for stability. Two different forms of domain-swapped dimers may coexist in solution (PMID:12121648) in which both subunits of the homodimer participate in coordination of each metal ion and formation of the U-shaped active sites in the enzyme (PMID:24004181). The complex is predominantly dimeric in solution (gel filtration) (PMID:12121648).
Chain A:
N/A
Chain B:
N/A
Surface and contacts features:
Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap). Download the CIF file (.cif)
Download this entry's XML file (.xml)
Download this entry's JSON file (.json)
