1p0c
From Proteopedia
(New page: 200px<br /><applet load="1p0c" size="450" color="white" frame="true" align="right" spinBox="true" caption="1p0c, resolution 2.2Å" /> '''Crystal Structure of ...) |
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| - | [[Image:1p0c.jpg|left|200px]]<br /><applet load="1p0c" size=" | + | [[Image:1p0c.jpg|left|200px]]<br /><applet load="1p0c" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1p0c, resolution 2.2Å" /> | caption="1p0c, resolution 2.2Å" /> | ||
'''Crystal Structure of the NADP(H)-Dependent Vertebrate Alcohol Dehydrogenase (ADH8)'''<br /> | '''Crystal Structure of the NADP(H)-Dependent Vertebrate Alcohol Dehydrogenase (ADH8)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The amphibian enzyme ADH8, previously named class IV-like, is the only | + | The amphibian enzyme ADH8, previously named class IV-like, is the only known vertebrate alcohol dehydrogenase (ADH) with specificity towards NADP(H). The three-dimensional structures of ADH8 and of the binary complex ADH8-NADP(+) have been now determined and refined to resolutions of 2.2A and 1.8A, respectively. The coenzyme and substrate specificity of ADH8, that has 50-65% sequence identity with vertebrate NAD(H)-dependent ADHs, suggest a role in aldehyde reduction probably as a retinal reductase. The large volume of the substrate-binding pocket can explain both the high catalytic efficiency of ADH8 with retinoids and the high K(m) value for ethanol. Preference of NADP(H) appears to be achieved by the presence in ADH8 of the triad Gly223-Thr224-His225 and the recruitment of conserved Lys228, which define a binding pocket for the terminal phosphate group of the cofactor. NADP(H) binds to ADH8 in an extended conformation that superimposes well with the NAD(H) molecules found in NAD(H)-dependent ADH complexes. No additional reshaping of the dinucleotide-binding site is observed which explains why NAD(H) can also be used as a cofactor by ADH8. The structural features support the classification of ADH8 as an independent ADH class. |
==About this Structure== | ==About this Structure== | ||
| - | 1P0C is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rana_porosa Rana porosa] with ZN, PO4 and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Alcohol_dehydrogenase_(NADP(+)) Alcohol dehydrogenase (NADP(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.2 1.1.1.2] Full crystallographic information is available from [http:// | + | 1P0C is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rana_porosa Rana porosa] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=PO4:'>PO4</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Alcohol_dehydrogenase_(NADP(+)) Alcohol dehydrogenase (NADP(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.2 1.1.1.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P0C OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Farres, J.]] | [[Category: Farres, J.]] | ||
[[Category: Fita, I.]] | [[Category: Fita, I.]] | ||
| - | [[Category: Ochoa, W | + | [[Category: Ochoa, W F.]] |
[[Category: Pares, X.]] | [[Category: Pares, X.]] | ||
[[Category: Rosell, A.]] | [[Category: Rosell, A.]] | ||
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[[Category: nadp(h)-dependent]] | [[Category: nadp(h)-dependent]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:23:41 2008'' |
Revision as of 12:23, 21 February 2008
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Crystal Structure of the NADP(H)-Dependent Vertebrate Alcohol Dehydrogenase (ADH8)
Overview
The amphibian enzyme ADH8, previously named class IV-like, is the only known vertebrate alcohol dehydrogenase (ADH) with specificity towards NADP(H). The three-dimensional structures of ADH8 and of the binary complex ADH8-NADP(+) have been now determined and refined to resolutions of 2.2A and 1.8A, respectively. The coenzyme and substrate specificity of ADH8, that has 50-65% sequence identity with vertebrate NAD(H)-dependent ADHs, suggest a role in aldehyde reduction probably as a retinal reductase. The large volume of the substrate-binding pocket can explain both the high catalytic efficiency of ADH8 with retinoids and the high K(m) value for ethanol. Preference of NADP(H) appears to be achieved by the presence in ADH8 of the triad Gly223-Thr224-His225 and the recruitment of conserved Lys228, which define a binding pocket for the terminal phosphate group of the cofactor. NADP(H) binds to ADH8 in an extended conformation that superimposes well with the NAD(H) molecules found in NAD(H)-dependent ADH complexes. No additional reshaping of the dinucleotide-binding site is observed which explains why NAD(H) can also be used as a cofactor by ADH8. The structural features support the classification of ADH8 as an independent ADH class.
About this Structure
1P0C is a Single protein structure of sequence from Rana porosa with , and as ligands. Active as Alcohol dehydrogenase (NADP(+)), with EC number 1.1.1.2 Full crystallographic information is available from OCA.
Reference
Crystal structure of the vertebrate NADP(H)-dependent alcohol dehydrogenase (ADH8)., Rosell A, Valencia E, Pares X, Fita I, Farres J, Ochoa WF, J Mol Biol. 2003 Jun 27;330(1):75-85. PMID:12818203
Page seeded by OCA on Thu Feb 21 14:23:41 2008
Categories: Alcohol dehydrogenase (NADP(+)) | Rana porosa | Single protein | Farres, J. | Fita, I. | Ochoa, W F. | Pares, X. | Rosell, A. | Valencia, E. | GOL | PO4 | ZN | Adh topology | Nadp(h)-dependent
