Database accession: MF7000458
Name: Fosfomycin Resistance Protein A (FosA) with Tl
PDB ID: 1lqo
Experimental method: X-ray (2.00 Å)
Assembly: Homodimer
Source organism: Pseudomonas aeruginosa
Primary publication of the structure:
Rife CL, Pharris RE, Newcomer ME, Armstrong RN
Crystal structure of a genomically encoded fosfomycin resistance protein (FosA) at 1.19 A resolution by MAD phasing off the L-III edge of Tl(+).
(2002) J. Am. Chem. Soc. 124: 11001-3
PMID: 12224946
Abstract:
The fosfomycin resistance protein (FosA) catalyzes the Mn(II)- and K+-dependent addition of glutathione to the oxirane of the antibiotic fosfomycin. The crystal structure of FosA from Pseudomonas aeruginosa was solved at a resolution of 1.19 A by multiwavelength anomalous diffraction at the L-III edge of a Tl+ derivative. The structure solution took advantage of the ability of Tl+ to substitute for K+. The existence of multiple Tl sites in the asymmetric unit suggests that this may be a generally useful technique for phasing protein crystal structures. A 1.35 A resolution structure with phosphate bound in the active site shows that the Mn(II) center has a rare four-coordinate geometry. The structure of the fosfomycin complex at 1.19 A resolution indicates that the Mn(II) center is close to five-coordinate with trigonal bipyramidal geometry and a ligand set consisting of two histidines (H7 and H64) and one phosphonate oxygen occupying the equatorial sites and the carboxylate of E110 at one of the apical sites. The oxirane oxygen of the substrate is located at the other apical site but is 0.2 A beyond the average Mn-O distance for five-coordinate Mn(II). The Mn(II) center is proposed to stabilize the alkoxide in the transition state, while the nearby hydroxyl group of T9 acts as a proton donor in the reaction. The K+ ion located 6.5 A from the Mn(II) appears to help orient the substrate for nucleophilic attack.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
glutathione transferase activity glutathione transferase activity
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: Glutathione transferase FosA
Source organism: Pseudomonas aeruginosa
Length: 135 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMLTGLNHLTLAVADLPASIAFYRDLLGFRLEARWDQGAYLELGSLWLCLSREPQYGGPAADYTHYAFGIAAADFARFAAQLRAHGVREWKQNRSEGDSFYFLDPDGHRLEAHVGDLRSRLAACRQAPYAGMRFAD
UniProtKB AC: Q9I4K6 (positions: 1-134)
Coverage: 99%
Name: Glutathione transferase FosA
Source organism: Pseudomonas aeruginosa
Length: 135 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMLTGLNHLTLAVADLPASIAFYRDLLGFRLEARWDQGAYLELGSLWLCLSREPQYGGPAADYTHYAFGIAAADFARFAAQLRAHGVREWKQNRSEGDSFYFLDPDGHRLEAHVGDLRSRLAACRQAPYAGMRFAD
UniProtKB AC: Q9I4K6 (positions: 1-134)
Coverage: 99%
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)
