1d1s
From Proteopedia
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|PDB= 1d1s |SIZE=350|CAPTION= <scene name='initialview01'>1d1s</scene>, resolution 2.5Å | |PDB= 1d1s |SIZE=350|CAPTION= <scene name='initialview01'>1d1s</scene>, resolution 2.5Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> |
| - | |ACTIVITY= [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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1agn|1AGN]], [[1d1t|1D1T]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1d1s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1d1s OCA], [http://www.ebi.ac.uk/pdbsum/1d1s PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1d1s RCSB]</span> | ||
}} | }} | ||
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[[Category: Hurley, T D.]] | [[Category: Hurley, T D.]] | ||
[[Category: Xie, P T.]] | [[Category: Xie, P T.]] | ||
| - | [[Category: ACT]] | ||
| - | [[Category: CAC]] | ||
| - | [[Category: NAD]] | ||
| - | [[Category: ZN]] | ||
[[Category: rossman or dinucleotide fold]] | [[Category: rossman or dinucleotide fold]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:32:50 2008'' |
Revision as of 16:32, 30 March 2008
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| , resolution 2.5Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , | ||||||
| Activity: | Alcohol dehydrogenase, with EC number 1.1.1.1 | ||||||
| Related: | 1AGN, 1D1T
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
WILD-TYPE HUMAN SIGMA (CLASS IV) ALCOHOL DEHYDROGENASE
Overview
Pyrazole and its 4-alkyl substituted derivatives are potent inhibitors for many alcohol dehydrogenases. However, the human sigma sigma isoenzyme exhibits a 580-fold lower affinity for 4-methylpyrazole than does the human beta1beta1 isoenzyme, with which it shares 69% sequence identity. In this study, structural and kinetic studies were utilized in an effort to identify key structural features that affect the binding of 4-methylpyrazole in human alcohol dehydrogenase isoenzymes. We have extended the resolution of the human sigma sigma alcohol dehydrogenase (ADH) isoenzyme to 2.5 A resolution. Comparison of this structure to the human beta1beta1 isoenzyme structure indicated that the side-chain position for Met141 in sigma sigma ADH might interfere with 4-methylpyrazole binding. Mutation of Met141 in sigma sigma ADH to Leu (sigma141L) lowers the Ki for 4-methylpyrazole from 350 to 10 microM, while having a much smaller effect on the Ki for pyrazole. Thus, the mutagenesis results show that the residue at position 141, which lines the substrate-binding pocket at a position close to the methyl group of 4-methylpyrazole, directly affects the binding of the inhibitor. To rule out nonspecific structural changes due to the mutation, the X-ray structure of the sigma141L mutant enzyme was determined to 2.4 A resolution. The three-dimensional structure of the mutant enzyme is identical to the wild-type enzyme, with the exception of the residue at position 141. Thus, the differences in 4-methylpyrazole binding between the mutant and wild-type sigma sigma ADH isoenzymes can be completely ascribed to the local changes in the topology of the substrate binding site, and provides an explanation for the class-specific differences in 4-methylpyrazole binding to the human ADH isoenzymes.
About this Structure
1D1S is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Methionine-141 directly influences the binding of 4-methylpyrazole in human sigma sigma alcohol dehydrogenase., Xie PT, Hurley TD, Protein Sci. 1999 Dec;8(12):2639-44. PMID:10631979
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