1ju9
From Proteopedia
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| - | + | {{STRUCTURE_1ju9| PDB=1ju9 | SCENE= }} | |
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'''HORSE LIVER ALCOHOL DEHYDROGENASE VAL292SER MUTANT''' | '''HORSE LIVER ALCOHOL DEHYDROGENASE VAL292SER MUTANT''' | ||
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[[Category: Ramaswamy, S.]] | [[Category: Ramaswamy, S.]] | ||
[[Category: Rubach, J K.]] | [[Category: Rubach, J K.]] | ||
| - | [[Category: | + | [[Category: Alcohol]] |
| - | [[Category: | + | [[Category: Dehydrogenase]] |
| - | [[Category: | + | [[Category: Mutant]] |
| - | [[Category: | + | [[Category: Nicotinamide coenzyme]] |
| - | [[Category: | + | [[Category: Oxidoreductase]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 21:55:52 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 18:55, 2 May 2008
HORSE LIVER ALCOHOL DEHYDROGENASE VAL292SER MUTANT
Overview
The participation of Val-292 in catalysis by alcohol dehydrogenase and the involvement of dynamics were investigated. Val-292 interacts with the nicotinamide ring of the bound coenzyme and may facilitate hydride transfer. The substitution of Val-292 with Ser (V292S) increases the dissociation constants for the coenzymes (NAD(+) by 50-fold, NADH by 75-fold) and the turnover numbers by 3-7-fold. The V292S enzyme crystallized in the presence of NAD(+) and 2,3,4,5,6-pentafluorobenzyl alcohol has an open conformation similar to the structure of the wild-type apo-enzyme, rather than the closed conformation observed for ternary complexes with wild-type enzyme. The V292S substitution perturbs the conformational equilibrium of the enzyme and decreases the kinetic complexity, which permits study of the hydride transfer step with steady-state kinetics. Eyring plots show that the DeltaH for the oxidation (V(1)) of the protio and deuterio benzyl alcohols is 13 kcal/mol and that the kinetic isotope effect of 4.1 is essentially temperature-independent. Eyring plots for the catalytic efficiency for reduction of benzaldehyde (V(2)/K(p)) with NADH or NADD are distinctly convex, being temperature-dependent from 5 to 25 degrees C and temperature-independent from 25 to 50 degrees C; the kinetic isotope effect of 3.2 for V(2)/K(p) is essentially independent of the temperature. The temperature dependencies and isotope effects for V(1) and V(2)/K(p) are not adequately explained by semiclassical transition state theory and are better explained by hydride transfer occurring through vibrationally assisted tunneling.
About this Structure
1JU9 is a Single protein structure of sequence from Equus caballus. Full crystallographic information is available from OCA.
Reference
Contributions of valine-292 in the nicotinamide binding site of liver alcohol dehydrogenase and dynamics to catalysis., Rubach JK, Ramaswamy S, Plapp BV, Biochemistry. 2001 Oct 23;40(42):12686-94. PMID:11601993 Page seeded by OCA on Fri May 2 21:55:52 2008
