4TO8

Methicillin-Resistant Staphylococcus Aureus Class IIb Fructose 1,6-Bisphosphate Aldolase

Summary for 4TO8

• Entry DOI: 10.2210/pdb4to8/pdb
• Descriptor: Fructose-1,6-bisphosphate aldolase, class II, ZINC ION, CITRATE ANION, ... (4 entities in total)
• Functional Keywords: zinc enzyme, methicillin resistant, aldol condensation, glycolysis, lyase, metal-binding
• Biological source: Staphylococcus aureus
• Total number of polymer chains: 2
• Total formula weight: 63910.80

Authors

Capodagli, G.C.,Pegan, S.D. (deposition date: 2014-06-05, release date: 2014-11-26, Last modification date: 2023-12-27)

Primary citation

Capodagli, G.C.,Lee, S.A.,Boehm, K.J.,Brady, K.M.,Pegan, S.D.
Structural and Functional Characterization of Methicillin-Resistant Staphylococcus aureus's Class IIb Fructose 1,6-Bisphosphate Aldolase.
Biochemistry, 53:7604-7614, 2014

PubMed Abstract: 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. Together 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.

PubMed: 25390935
DOI: 10.1021/bi501141t

Experimental method

X-RAY DIFFRACTION (2.1 Å)