Structure of the Type III Pantothenate Kinase from Bacillus Anthracis at 2.0 A Resolution: Implications for Coenzyme A-Dependent Redox Biology
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 {angstrom}, 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.
- Research Organization:
- Brookhaven National Laboratory (BNL) National Synchrotron Light Source
- Sponsoring Organization:
- Doe - Office Of Science
- DOE Contract Number:
- AC02-98CH10886
- OSTI ID:
- 930265
- Report Number(s):
- BNL--80958-2008-JA
- Journal Information:
- Biochemistry, Journal Name: Biochemistry Journal Issue: 11 Vol. 46; ISSN 0006-2960
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ACETATES
ATP
BACILLUS
BACTERIA
BIOCHEMISTRY
BIOLOGY
COENZYMES
CONVERSION
CRYSTAL STRUCTURE
DATA
DISPERSIONS
ENZYMES
ESCHERICHIA COLI
FEEDBACK
INHIBITION
INTERFACES
OXIDOREDUCTASES
PHOSPHOTRANSFERASES
PROTEINS
PYRIDYLAZONAPHTHOL
RESOLUTION
SACCHAROSE
STAPHYLOCOCCUS
SUBSTRATES
THIOLS
WEIGHT
national synchrotron light source