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| | {{STRUCTURE_1qv6| PDB=1qv6 | SCENE= }} | | {{STRUCTURE_1qv6| PDB=1qv6 | SCENE= }} |
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| - | '''HORSE LIVER ALCOHOL DEHYDROGENASE HIS51GLN/LYS228ARG MUTANT COMPLEXED WITH NAD+ AND 2,4-DIFLUOROBENZYL ALCOHOL'''
| + | ===HORSE LIVER ALCOHOL DEHYDROGENASE HIS51GLN/LYS228ARG MUTANT COMPLEXED WITH NAD+ AND 2,4-DIFLUOROBENZYL ALCOHOL=== |
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| - | ==Overview==
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| - | Histidine-51 in horse liver alcohol dehydrogenase (ADH) is part of a hydrogen-bonded system that appears to facilitate deprotonation of the hydroxyl group of water or alcohol ligated to the catalytic zinc. The contribution of His-51 to catalysis was studied by characterizing ADH with His-51 substituted with Gln (H51Q). The steady-state kinetic constants for ethanol oxidation and acetaldehyde reduction at pH 8 are similar for wild-type and H51Q enzymes. In contrast, the H51Q substitution significantly shifts the pH dependencies for steady-state and transient reactions and decreases by 11-fold the rate constant for the transient oxidation of ethanol at pH 8. Modest substrate deuterium isotope effects indicate that hydride transfer only partially limits the transient oxidation and turnover. Transient data show that the H51Q substitution significantly decreases the rate of isomerization of the enzyme-NAD(+) complex and becomes a limiting step for ethanol oxidation. Isomerization of the enzyme-NAD(+) complex is rate limiting for acetaldehyde reduction catalyzed by the wild-type enzyme, but release of alcohol is limiting for the H51Q enzyme. X-ray crystallography of doubly substituted His51Gln:Lys228Arg ADH complexed with NAD(+) and 2,3- or 2,4-difluorobenzyl alcohol shows that Gln-51 isosterically replaces histidine in interactions with the nicotinamide ribose of the coenzyme and that Arg-228 interacts with the adenosine monophosphate of the coenzyme without affecting the protein conformation. The difluorobenzyl alcohols bind in one conformation. His-51 participates in, but is not essential for, proton transfers in the mechanism.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_15023053}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 15023053 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_15023053}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Horse liver]] | | [[Category: Horse liver]] |
| | [[Category: Nicotinamide coenzyme]] | | [[Category: Nicotinamide coenzyme]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 06:44:24 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 06:05:01 2008'' |
Revision as of 03:05, 29 July 2008
Template:STRUCTURE 1qv6
HORSE LIVER ALCOHOL DEHYDROGENASE HIS51GLN/LYS228ARG MUTANT COMPLEXED WITH NAD+ AND 2,4-DIFLUOROBENZYL ALCOHOL
Template:ABSTRACT PUBMED 15023053
About this Structure
1QV6 is a Single protein structure of sequence from Equus caballus. Full crystallographic information is available from OCA.
Reference
Participation of histidine-51 in catalysis by horse liver alcohol dehydrogenase., LeBrun LA, Park DH, Ramaswamy S, Plapp BV, Biochemistry. 2004 Mar 23;43(11):3014-26. PMID:15023053
Page seeded by OCA on Tue Jul 29 06:05:01 2008
