Actions for Structural and functional characterization of methicillin-resistant <i>Staphylococcus aureus’s<
Structural and functional characterization of methicillin-resistant <i>Staphylococcus aureus’s</i> class IIb fructose 1,6-bisphosphate aldolase [electronic resource].
- Published
- Washington, D.C. : United States. Dept. of Energy. Office of Basic Energy Sciences, 2014.
Oak Ridge, Tenn. : Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy - Physical Description
- pages 7,604-7,614 : digital, PDF file
- Additional Creators
- United States. Department of Energy. Office of Basic Energy Sciences and United States. Department of Energy. Office of Scientific and Technical Information
Access Online
- Restrictions on Access
- Free-to-read Unrestricted online access
- Summary
- Staphylococcus aureus is one of the most common nosocomial sources of soft-tissue and skin infections and has more recently become prevalent in the community setting as well. Since the use of penicillins to combat S. aureus infections in the 1940s, the bacterium has been notorious for developing resistances to antibiotics, such as methicillin-resistant Staphylococcus aureus (MRSA). With the persistence of MRSA as well as many other drug resistant bacteria and parasites, there is a growing need to focus on new pharmacological targets. Recently, class II fructose 1,6-bisphosphate aldolases (FBAs) have garnered attention to fill this role. Regrettably, scarce biochemical data and no structural data are currently available for the class II FBA found in MRSA (SaFBA). With the recent finding of a flexible active site zinc-binding loop (Z-Loop) in class IIa FBAs and its potential for broad spectrum class II FBA inhibition, the lack of information regarding this feature of class IIb FBAs, such as SaFBA, has been limiting for further Z-loop inhibitor development. Therefore, we elucidated the crystal structure of SaFBA to 2.1 Å allowing for a more direct structural analysis of SaFBA. Furthermore, we determined the KM for one of SaFBA’s substrates, fructose 1,6-bisphosphate, as well as performed mode of inhibition studies for an inhibitor that takes advantage of the Z-loop’s flexibility. Altogether the data offers insight into a class IIb FBA from a pervasively drug resistant bacterium and a comparison of Z-loops and other features between the different subtypes of class II FBAs.
- Report Numbers
- E 1.99:1345591
- Subject(s)
- Note
- Published through SciTech Connect.
11/12/2014.
Biochemistry 53 48 ISSN 0006-2960 AM
Glenn C. Capodagli; Stephen A. Lee; Kyle J. Boehm; Kristin M. Brady; Scott D. Pegan.
Univ. of Denver, Denver, CO (United States)
Univ. of Georgia, Athens, GA (United States) - Funding Information
- AC02-05CH11231
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