Crystal Structure of the YjeE Protein from Haemophilus Influenzae: A Putative Atpase Involved in Cell Wall Synthesis

Published

August 1, 2002

Author(s)

A Teplyakov, G Obmolova, M Tordova, N Thanki, N Bonander, E Eisenstein, A J. Howard, G L. Gilliland

Abstract

A hypothetical protein encoded by the gene YjeE of Haemophilus influenzae was selected as part of a structural genomics project, for X-ray analysis to assist with the functional assignment. The protein is considered essential to bacteria since the gene is present in virtually all bacterial genomes, but not in those of archaea or eukaryotes. The amino acid sequence shows no homology to other proteins. However, the presence of the Walker A motif G-X-X-X-X-G-K-T indicates the possibility of a nucleotide-binding protein. The YjeE protein was cloned, expressed, and the crystal structure determined by the MAD method at 1.7- resolution. The protein has a nucleotide-binding fold with the P-loop typical for many ATPases and GTPases, although the topology of the b-sheet is unique. Crystallization experiments and nucleotide modeling indicate the preference of YjeE to ATP rather than to GTP. The observation of a hydrolyzed nucleotide (ADP) in the active site implies ATPase activity of YjeE. Structural comparison of YjeE with the P-loop proteins from the 14 known families shows that it represents a new class of P-loop ATPases. The phylogenetic pattern of YjeE strongly suggests its involvement in cell wall biosynthesis. The protein is likely to be an ATP-dependent regulator of peptidoglycan metabolism given the distribution of conserved residues and structural features typical for 'molecular switches'. As such, it may be a promising target for new antibiotics.

Citation

Proteins-Structure Function And Genetics

Volume

48

Issue

2

Pub Type

Journals

Keywords

ATPase, cell wall synthesis, nucleotide binding fold structural genom

Citation

Teplyakov, A. , Obmolova, G. , Tordova, M. , Thanki, N. , Bonander, N. , Eisenstein, E. , Howard, A. and Gilliland, G. (2002), Crystal Structure of the YjeE Protein from Haemophilus Influenzae: A Putative Atpase Involved in Cell Wall Synthesis, Proteins-Structure Function And Genetics (Accessed December 13, 2024)