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. 2004 May;13(5):1260-5.
doi: 10.1110/ps.03585004. Epub 2004 Apr 9.

Structure of fosfomycin resistance protein FosA from transposon Tn2921

Svetlana Pakhomova  1 , Chris L Rife, Richard N Armstrong, Marcia E Newcomer
Affiliations

Structure of fosfomycin resistance protein FosA from transposon Tn2921

Svetlana Pakhomova et al. Protein Sci. 2004 May.

Abstract

The crystal structure of fosfomycin resistance protein FosA from transposon Tn2921 has been established at a resolution of 2.5 A. The protein crystallized without bound Mn(II) and K+, ions crucial for efficient catalysis, providing a structure of the apo enzyme. The protein maintains the three-dimensional domain-swapped arrangement of the paired betaalphabetabetabeta-motifs observed in the genomically encoded homologous enzyme from Pseudomonas aeruginosa (PA1129). The basic architecture of the active site is also maintained, despite the absence of the catalytically essential Mn(II). However, the absence of K+, which has been shown to enhance enzymatic activity, appears to contribute to conformational heterogeneity in the K(+)-binding loops.

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Figures

Figure 1.
Figure 1.
Sequence alignment between FosA and PA1129. The image was generated using the program ESPript (Gouet et al. 1999).
Figure 2.
Figure 2.
View of the FosA dimer. (A) A stereo view of FosA dimer along a twofold NCS symmetry axis with bound sulfate ions and glycerol molecules. Monomers A and B are shown in green and yellow, respectively. (B) A stereo view of superposition of FosA (magenta) and PA1129 (blue) dimers. (C) A trimer of dimers as observed in the asymmetric unit of the FosA structure. Pictures 2–4 were made by using SETOR (Evans 1993).
Figure 3.
Figure 3.
A stereo view of superposition of K+ loops from six independent molecules of metal-free (FosA, light gray) and metal-bound (PA1129, dark gray) enzymes. The K+ loops in the metal-free enzyme adopt a variety of conformations in the six monomers of the asymmetric unit. The side chain of glutamate 98 is included in the loops that represent the extremes of the spectrum of conformations.
Figure 4.
Figure 4.
(A) The active site cavity of subunit A of FosA with bound sulfate ions. Superimposed active site residues, Mn(II), fosfomycin, and K+ loop from PA1129 FosA are shown in pink. (B) Close-up stereo view of the active site.
Scheme 1
Scheme 1
See this image and copyright information in PMC

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References

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