2H3G

Structure of the Type III Pantothenate Kinase (CoaX) from Bacillus Anthracis

Summary for 2H3G

• Entry DOI: 10.2210/pdb2h3g/pdb
• Descriptor: BIOSYNTHETIC PROTEIN, 1,2-ETHANEDIOL (3 entities in total)
• Functional Keywords: pantothenate kinase, bacillus anthracis, anthrax, type iii pantothenate kinase, coax, coaa, askha, biosynthetic protein
• Biological source: Bacillus anthracis str.
• Cellular location: Cytoplasm : Q73FE2
• Total number of polymer chains: 1
• Total formula weight: 30019.70

Authors

Nicely, N.I. (deposition date: 2006-05-22, release date: 2007-03-20, Last modification date: 2024-02-14)

Primary citation

Nicely, N.I.,Parsonage, D.,Paige, C.,Newton, G.L.,Fahey, R.C.,Leonardi, R.,Jackowski, S.,Mallett, T.C.,Claiborne, A.
Structure of the Type III Pantothenate Kinase from Bacillus anthracis at 2.0 A Resolution: Implications for Coenzyme A-Dependent Redox Biology.
Biochemistry, 46:3234-3245, 2007

PubMed Abstract: Coenzyme A (CoASH) is the major low-molecular weight thiol in Staphylococcus aureus and a number of other bacteria; the crystal structure of the S. aureus coenzyme A-disulfide reductase (CoADR), which maintains the reduced intracellular state of CoASH, has recently been reported [Mallett, T.C., Wallen, J.R., Karplus, P.A., Sakai, H., Tsukihara, T., and Claiborne, A. (2006) Biochemistry 45, 11278-89]. In this report we demonstrate that CoASH is the major thiol in Bacillus anthracis; a bioinformatics analysis indicates that three of the four proteins responsible for the conversion of pantothenate (Pan) to CoASH in Escherichia coli are conserved in B. anthracis. In contrast, a novel type III pantothenate kinase (PanK) catalyzes the first committed step in the biosynthetic pathway in B. anthracis; unlike the E. coli type I PanK, this enzyme is not subject to feedback inhibition by CoASH. The crystal structure of B. anthracis PanK (BaPanK), solved using multiwavelength anomalous dispersion data and refined at a resolution of 2.0 A, demonstrates that BaPanK is a new member of the Acetate and Sugar Kinase/Hsc70/Actin (ASKHA) superfamily. The Pan and ATP substrates have been modeled into the active-site cleft; in addition to providing a clear rationale for the absence of CoASH inhibition, analysis of the Pan-binding pocket has led to the development of two new structure-based motifs (the PAN and INTERFACE motifs). Our analyses also suggest that the type III PanK in the spore-forming B. anthracis plays an essential role in the novel thiol/disulfide redox biology of this category A biodefense pathogen.

PubMed: 17323930
DOI: 10.1021/bi062299p

Experimental method

X-RAY DIFFRACTION (2 Å)