3QXH: Crystal Structure Of Dethiobiotin Synthetase (biod) From Helicobacter Pylori Complexed With Adp And 8-aminocaprylic Acid

Citation:
Abstract
Dethiobiotin synthetase (DTBS) is involved in the biosynthesis of biotin in bacteria, fungi, and plants. As humans lack this pathway, DTBS is a promising antimicrobial drug target. We determined structures of DTBS from Helicobacter pylori (hpDTBS) bound with cofactors and a substrate analog, and described its unique characteristics relative to other DTBS proteins. Comparison with bacterial DTBS orthologs revealed considerable structural differences in nucleotide recognition. The C-terminal region of DTBS proteins, which contains two nucleotide-recognition motifs, differs greatly among DTBS proteins from different species. The structure of hpDTBS revealed that this protein is unique and does not contain a C-terminal region containing one of the motifs. The single nucleotide-binding motif in hpDTBS is similar to its counterpart in GTPases; however, isothermal titration calorimetry binding studies showed that hpDTBS has a strong preference for ATP. The structural determinants of ATP specificity were assessed with X-ray crystallographic studies of hpDTBS.ATP and hpDTBS.GTP complexes. The unique mode of nucleotide recognition in hpDTBS makes this protein a good target for H. pylori-specific inhibitors of the biotin synthesis pathway.
PDB ID: 3QXHDownload
MMDB ID: 89583
PDB Deposition Date: 2011/3/1
Updated in MMDB: 2011/05
Experimental Method:
x-ray diffraction
Resolution: 1.36  Å
Source Organism:
Similar Structures:
Biological Unit for 3QXH: dimeric; determined by author and by software (PISA)
Molecular Components in 3QXH
Label Count Molecule
Proteins (2 molecules)
2
Dethiobiotin Synthetase(Gene symbol: HP0029)
Molecule annotation
Chemicals (20 molecules)
1
2
2
2
3
4
4
2
5
10
* Click molecule labels to explore molecular sequence information.

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