1yjq

Crystal structure of ketopantoate reductase in complex with NADP+

spinqualitylabelsall models 1yjq, resolution 2.09Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1yjq is a 1 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.09Å Ligands: ACT, MPD, NAP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PANE_ECOLI Catalyzes the NADPH-dependent reduction of ketopantoate into pantoic acid. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The NADPH-dependent reduction of ketopantoate to pantoate, catalyzed by ketopantoate reductase (KPR; EC 1.1.1.169), is essential for the biosynthesis of pantothenate (vitamin B(5)). Here we present the crystal structure of Escherichia coli KPR with NADP(+) bound, solved to 2.1 A resolution. The cofactor is bound in the active site cleft between the N-terminal Rossmann-fold domain and the C-terminal alpha-helical domain. The thermodynamics of cofactor and substrate binding were characterized by isothermal titration calorimetry. The dissociation constant for NADP(+) was found to be 6.5 muM, 20-fold larger than that for NADPH (0.34 muM). The difference is primarily due to the entropic term, suggesting favorable hydrophobic interactions of the more lipophilic nicotinamide ring in NADPH. Comparison of this binary complex structure with the previously studied apoenzyme reveals no evidence for large domain movements on cofactor binding. This observation is further supported both by molecular dynamics and by calorimetric analysis. A model of the ternary complex, based on the structure presented here, provides novel insights into the molecular mechanism of enzyme catalysis. We propose a conformational switch of the essential Lys176 from the "resting" state observed in our structure to an "active" state, to bind ketopantoate. Additionally, we identify the importance of Asn98 for substrate binding and enzyme catalysis. The crystal structure of Escherichia coli ketopantoate reductase with NADP+ bound.,Lobley CM, Ciulli A, Whitney HM, Williams G, Smith AG, Abell C, Blundell TL Biochemistry. 2005 Jun 28;44(25):8930-9. PMID:15966718 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA