4ng5

V203A horse liver alcohol dehydrogenase E complexed with NAD+ and 2,3,4,5,6-pentafluorobenzyl alcohol

spinqualitylabelsall models 4ng5, resolution 1.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ng5 is a 2 chain structure with sequence from Equus caballus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.1Å Ligands: MRD, NAJ, PFB, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ADH1E_HORSE Publication Abstract from PubMed A role for protein dynamics in enzymatic catalysis of hydrogen transfer has received substantial scientific support, but the connections between protein structure and catalysis remain to be established. Valine residues 203 and 207 are at the binding site for the nicotinamide ring of the coenzyme in liver alcohol dehydrogenase and have been suggested to facilitate catalysis with "protein-promoting vibrations" (PPV). We find that the V207A substitution has small effects on steady-state kinetic constants and the rate of hydrogen transfer; the introduced cavity is empty and is tolerated with minimal effects on structure (determined at 1.2 A for the complex with NAD(+) and 2,3,4,5,6-pentafluorobenzyl alcohol). Thus, no evidence is found to support a role for Val-207 in the dynamics of catalysis. The protein structures and ligand geometries (including donor-acceptor distances) in the V203A enzyme complexed with NAD(+) and 2,3,4,5,6-pentafluorobenzyl alcohol or 2,2,2-trifluoroethanol (determined at 1.1 A) are very similar to those for the wild-type enzyme, except that the introduced cavity accommodates a new water molecule that contacts the nicotinamide ring. The structures of the V203A enzyme complexes suggest, in contrast to previous studies, that the diminished tunneling and decreased rate of hydride transfer (16-fold, relative to that of the wild-type enzyme) are not due to differences in ground-state ligand geometries. The V203A substitution may alter the PPV and the reorganization energy for hydrogen transfer, but the protein scaffold and equilibrium thermal motions within the Michaelis complex may be more significant for enzyme catalysis. Effects of cavities at the nicotinamide binding site of liver alcohol dehydrogenase on structure, dynamics and catalysis.,Yahashiri A, Rubach JK, Plapp BV Biochemistry. 2014 Feb 11;53(5):881-94. doi: 10.1021/bi401583f. Epub 2014 Jan 30. PMID:24437493 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Alcohol dehydrogenase 3D structures

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