1hsz
From Proteopedia
(New page: 200px<br /> <applet load="1hsz" size="450" color="white" frame="true" align="right" spinBox="true" caption="1hsz, resolution 2.20Å" /> '''HUMAN BETA-1 ALCOHO...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1hsz.gif|left|200px]]<br /> | + | [[Image:1hsz.gif|left|200px]]<br /><applet load="1hsz" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1hsz" size=" | + | |
caption="1hsz, resolution 2.20Å" /> | caption="1hsz, resolution 2.20Å" /> | ||
'''HUMAN BETA-1 ALCOHOL DEHYDROGENASE (ADH1B*1)'''<br /> | '''HUMAN BETA-1 ALCOHOL DEHYDROGENASE (ADH1B*1)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | In contrast with other animal species, humans possess three distinct genes | + | In contrast with other animal species, humans possess three distinct genes for class I alcohol dehydrogenase and show polymorphic variation in the ADH1B and ADH1C genes. The three class I alcohol dehydrogenase isoenzymes share approximately 93% sequence identity but differ in their substrate specificity and their developmental expression. We report here the first three-dimensional structures for the ADH1A and ADH1C*2 gene products at 2.5 and 2.0 A, respectively, and the structure of the ADH1B*1 gene product in a binary complex with cofactor at 2.2 A. Not surprisingly, the overall structure of each isoenzyme is highly similar to the others. However, the substitution of Gly for Arg at position 47 in the ADH1A isoenzyme promotes a greater extent of domain closure in the ADH1A isoenzyme, whereas substitution at position 271 may account for the lower turnover rate for the ADH1C*2 isoenzyme relative to its polymorphic variant, ADH1C*1. The substrate-binding pockets of each isoenzyme possess a unique topology that dictates each isoenzyme's distinct but overlapping substrate preferences. ADH1*B1 has the most restrictive substrate-binding site near the catalytic zinc atom, whereas both ADH1A and ADH1C*2 possess amino acid substitutions that correlate with their better efficiency for the oxidation of secondary alcohols. These structures describe the nature of their individual substrate-binding pockets and will improve our understanding of how the metabolism of beverage ethanol affects the normal metabolic processes performed by these isoenzymes. |
==Disease== | ==Disease== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1HSZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN, PO4 and NAD as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Alcohol_dehydrogenase Alcohol dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.1 1.1.1.1] Full crystallographic information is available from [http:// | + | 1HSZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=PO4:'>PO4</scene> and <scene name='pdbligand=NAD:'>NAD</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Alcohol_dehydrogenase Alcohol dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.1 1.1.1.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HSZ OCA]. |
==Reference== | ==Reference== | ||
| Line 18: | Line 17: | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Gibbons, B | + | [[Category: Gibbons, B J.]] |
| - | [[Category: Hurley, T | + | [[Category: Hurley, T D.]] |
| - | [[Category: Niederhut, M | + | [[Category: Niederhut, M S.]] |
[[Category: Perez-Miller, S.]] | [[Category: Perez-Miller, S.]] | ||
[[Category: NAD]] | [[Category: NAD]] | ||
| Line 29: | Line 28: | ||
[[Category: zinc]] | [[Category: zinc]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:04:32 2008'' |
Revision as of 11:04, 21 February 2008
|
HUMAN BETA-1 ALCOHOL DEHYDROGENASE (ADH1B*1)
Contents |
Overview
In contrast with other animal species, humans possess three distinct genes for class I alcohol dehydrogenase and show polymorphic variation in the ADH1B and ADH1C genes. The three class I alcohol dehydrogenase isoenzymes share approximately 93% sequence identity but differ in their substrate specificity and their developmental expression. We report here the first three-dimensional structures for the ADH1A and ADH1C*2 gene products at 2.5 and 2.0 A, respectively, and the structure of the ADH1B*1 gene product in a binary complex with cofactor at 2.2 A. Not surprisingly, the overall structure of each isoenzyme is highly similar to the others. However, the substitution of Gly for Arg at position 47 in the ADH1A isoenzyme promotes a greater extent of domain closure in the ADH1A isoenzyme, whereas substitution at position 271 may account for the lower turnover rate for the ADH1C*2 isoenzyme relative to its polymorphic variant, ADH1C*1. The substrate-binding pockets of each isoenzyme possess a unique topology that dictates each isoenzyme's distinct but overlapping substrate preferences. ADH1*B1 has the most restrictive substrate-binding site near the catalytic zinc atom, whereas both ADH1A and ADH1C*2 possess amino acid substitutions that correlate with their better efficiency for the oxidation of secondary alcohols. These structures describe the nature of their individual substrate-binding pockets and will improve our understanding of how the metabolism of beverage ethanol affects the normal metabolic processes performed by these isoenzymes.
Disease
Known diseases associated with this structure: Alcoholism, susceptibility to OMIM:[103720]
About this Structure
1HSZ is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Alcohol dehydrogenase, with EC number 1.1.1.1 Full crystallographic information is available from OCA.
Reference
Three-dimensional structures of the three human class I alcohol dehydrogenases., Niederhut MS, Gibbons BJ, Perez-Miller S, Hurley TD, Protein Sci. 2001 Apr;10(4):697-706. PMID:11274460
Page seeded by OCA on Thu Feb 21 13:04:32 2008
Categories: Alcohol dehydrogenase | Homo sapiens | Single protein | Gibbons, B J. | Hurley, T D. | Niederhut, M S. | Perez-Miller, S. | NAD | PO4 | ZN | Rossmann fold | Zinc
