Structure of the ribosomal interacting GTPase YjeQ from the enterobacterial species Salmonella typhimurium.
The YjeQ class of P-loop GTPases assist in ribosome biogenesis and also bind to the 30S subunit of mature ribosomes. YjeQ ribosomal binding is GTP-dependent and thought to specifically direct protein synthesis, although the nature of the upstream signal causing this event in vivo is as yet unknown. The attenuating effect of YjeQ mutants on bacterial growth in Escherichia coli makes it a potential target for novel antimicrobial agents. In order to further explore the structure and function of YjeQ, the isolation, crystallization and structure determination of YjeQ from the enterobacterial species Salmonella typhimurium (StYjeQ) is reported. Whilst the overall StYjeQ fold is similar to those of the previously reported Thematoga maritima and Bacillus subtilis orthologues, particularly the GTPase domain, there are larger differences in the three OB folds. Although the zinc-finger secondary structure is conserved, significant sequence differences alter the nature of the external surface in each case and may reflect varying signalling pathways. Therefore, it may be easier to develop YjeQ-specific inhibitors that target the N- and C-terminal regions, disrupting the metabolic connectivity rather than the GTPase activity. The availability of coordinates for StYjeQ will provide a significantly improved basis for threading Gram-negative orthologue sequences and in silico compound-screening studies, with the potential for the development of species-selective drugs.
Nichols
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CE
Division of Structural Biology, The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, England.
Johnson
C
C
Lamb
H K
HK
Lockyer
M
M
Charles
I G
IG
Hawkins
A R
AR
Stammers
D K
DK
D000595:Amino Acid Sequence; D002151:Calorimetry; D003460:Crystallization; D018360:Crystallography, X-Ray; D020558:GTP Phosphohydrolases / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D012486:Salmonella typhimurium / Q000201:enzymology*; D016415:Sequence Alignment; D013816:Thermodynamics
D020558:GTP Phosphohydrolases