3QXC

Crystal structure of dethiobiotin synthetase (BioD) from Helicobacter pylori complexed with ATP

Summary for 3QXC

• Entry DOI: 10.2210/pdb3qxc/pdb
• Related: 2QMO 3MLE 3QXH 3QXJ 3QXS 3QXX 3QY0
• Descriptor: Dethiobiotin synthetase, ADENOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION, ... (8 entities in total)
• Functional Keywords: dtbs, dethiobiotin synthetase, structural genomics, atp binding, psi-biology, protein structure initiative, midwest center for structural genomics, mcsg, ligase
• Biological source: Helicobacter pylori
• Cellular location: Cytoplasm (By similarity): O24872
• Total number of polymer chains: 1
• Total formula weight: 28684.61

Authors

Porebski, P.J.,Klimecka, M.M.,Chruszcz, M.,Murzyn, K.,Joachimiak, A.,Minor, W.,Midwest Center for Structural Genomics (MCSG) (deposition date: 2011-03-01, release date: 2011-03-30, Last modification date: 2023-09-13)

Primary citation

Porebski, P.J.,Klimecka, M.,Chruszcz, M.,Nicholls, R.A.,Murzyn, K.,Cuff, M.E.,Xu, X.,Cymborowski, M.,Murshudov, G.N.,Savchenko, A.,Edwards, A.,Minor, W.
Structural characterization of Helicobacter pylori dethiobiotin synthetase reveals differences between family members.
Febs J., 279:1093-1105, 2012

PubMed 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.

PubMed: 22284390
DOI: 10.1111/j.1742-4658.2012.08506.x

Experimental method

X-RAY DIFFRACTION (1.34 Å)