3p4p

Crystal structure of Menaquinol:fumarate oxidoreductase in complex with fumarate

spinqualitylabelsall models 3p4p, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3p4p is a 8 chain structure with sequence from Escherichia coli 042, Escherichia coli 536 and Escherichia coli DH1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.8Å Ligands: FAD, FES, FUM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function FRDA_ECOLI Two distinct, membrane-bound, FAD-containing enzymes are responsible for the catalysis of fumarate and succinate interconversion; the fumarate reductase is used in anaerobic growth, and the succinate dehydrogenase is used in aerobic growth. Publication Abstract from PubMed Complex II superfamily members catalyze the kinetically difficult interconversion of succinate and fumarate. Due to the relative simplicity of complex II substrates and their similarity to other biologically abundant small molecules, substrate specificity presents a challenge in this system. In order to identify determinants for on-pathway catalysis, off-pathway catalysis, and enzyme inhibition, crystal structures of Escherichia coli menaquinol:fumarate reductase (QFR), a complex II superfamily member, were determined bound to the substrate, fumarate, and the inhibitors oxaloacetate, glutarate, and 3-nitropropionate. Optical difference spectroscopy and computational modeling support a model where QFR twists the dicarboxylate, activating it for catalysis. Orientation of the C2-C3 double bond of activated fumarate parallel to the C(4a)-N5 bond of FAD allows orbital overlap between the substrate and the cofactor, priming the substrate for nucleophilic attack. Off-pathway catalysis, such as the conversion of malate to oxaloacetate or the activation of the toxin 3-nitropropionate may occur when inhibitors bind with a similarly activated bond in the same position. Conversely, inhibitors that do not orient an activatable bond in this manner, such as glutarate and citrate, are excluded from catalysis and act as inhibitors of substrate binding. These results support a model where electronic interactions via geometric constraint and orbital steering underlie catalysis by QFR. Geometric restraint drives on- and off-pathway catalysis by the Escherichia coli menaquinol:fumarate reductase.,Tomasiak TM, Archuleta TL, Andrell J, Lunz-Chavez C, Davis TA, Sarwar M, Ham AJ, McDonald WH, Yankovskaya V, Stern HA, Johnston JN, McLashina E, Cecchini G, Iverson TM J Biol Chem. 2010 Nov 23. PMID:21098488 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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