Structural highlights
FunctionPublication Abstract from PubMedCapsular polysaccharide is an important virulence factor during infections by bacterium Staphylococcus aureus. The enzyme CapF is an attractive therapeutic candidate belonging to the biosynthetic route of CP of pathogenic strains of S. aureus. Herein we report two independent crystal structures of CapF in an open form of the apo-enzyme. CapF is a homodimer displaying a characteristic dumbbell-shape composed of two domains. The N-terminal domain (residues 1-252) adopts a Rossmann fold belonging to the short-chain dehydrogenase/reductase family of proteins. The C-terminal domain (residues 252-369) displays a standard cupin fold with a Zn2+ ion bound deep in the binding pocket of the beta-barrel. Functional and thermodynamic analyses indicated that each domain catalyzes separate enzymatic reactions. The cupin domain is necessary for the C3-epimerization of UDP-4-hexulose. Meanwhile, the N-terminal domain catalyzes the NADPH-dependent reduction of the intermediate species generated by the cupin domain. Binding analysis by ITC revealed a fascinating thermodynamic switch governing the attachment and release of coenzyme NADPH during each catalytic cycle. Binding of coenzyme to CapF facilitates an order/disorder transition in the catalytic loop of the reductase (N-terminal) domain. We expect our study will improve the general understanding of the synthesis of capsular polysaccharide in S. aureus, and will aid in the design of new therapeutic agents against this pathogenic bacterium. Crystal Structure of Enzyme CapF of Staphylococcus aureus Reveals a Unique Architecture Composed of Two Functional Domains.,Miyafusa T, Caaveiro JM, Tanaka Y, Tsumoto K Biochem J. 2012 Feb 9. PMID:22320426[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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