4lv4

A noncompetitive inhibitor for M. tuberculosis's class IIa fructose 1,6-bisphosphate aldolaseA noncompetitive inhibitor for M. tuberculosis's class IIa fructose 1,6-bisphosphate aldolase

Structural highlights 4lv4 is a 1 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.08Å Ligands: , , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ALF_MYCTU Catalyzes the aldol condensation of dihydroxyacetone phosphate (DHAP or glycerone-phosphate) with glyceraldehyde 3-phosphate (G3P) to form fructose 1,6-bisphosphate (FBP) in gluconeogenesis and the reverse reaction in glycolysis (By similarity). Publication Abstract from PubMed Class II fructose 1,6-bisphosphate aldolase (FBA) is an enzyme critical for bacterial, fungal, and protozoan glycolysis/gluconeogenesis. Importantly, humans lack this type of aldolase, having instead a class I FBA that is structurally and mechanistically distinct from class II FBAs. As such, class II FBA is considered a putative pharmacological target for the development of novel antibiotics against pathogenic bacteria such as Mycobacterium tuberculosis, the causative agent for tuberculosis (TB). To date, several competitive class II FBA substrate mimic-styled inhibitors have been developed; however, they lack either specificity, potency, or properties that limit their potential as possible therapeutics. Recently, through the use of enzymatic and structure-based assisted screening, we identified 8-hydroxyquinoline carboxylic acid (HCA) that has an IC50 of 10 +/- 1 muM for the class II FBA present in M. tuberculosis (MtFBA). As opposed to previous inhibitors, HCA behaves in a noncompetitive manner, shows no inhibitory properties toward human and rabbit class I FBAs, and possesses anti-TB properties. Furthermore, we were able to determine the crystal structure of HCA bound to MtFBA to 2.1 A. HCA also demonstrates inhibitory effects for other class II FBAs, including pathogenic bacteria such as methicillin-resistant Staphylococcus aureus. With its broad-spectrum potential, unique inhibitory characteristics, and flexibility of functionalization, the HCA scaffold likely represents an important advancement in the development of class II FBA inhibitors that can serve as viable preclinical candidates. A Noncompetitive Inhibitor for Mycobacterium tuberculosis's Class IIa Fructose 1,6-Bisphosphate Aldolase.,Capodagli GC, Sedhom WG, Jackson M, Ahrendt KA, Pegan SD Biochemistry. 2013 Dec 24. PMID:24325645 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aldolase 3D structures

spinqualitylabelsall models 4lv4, resolution 2.08Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image