1hld
From Proteopedia
(New page: 200px<br /><applet load="1hld" size="450" color="white" frame="true" align="right" spinBox="true" caption="1hld, resolution 2.1Å" /> '''STRUCTURES OF HORSE L...) |
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| - | [[Image:1hld.jpg|left|200px]]<br /><applet load="1hld" size=" | + | [[Image:1hld.jpg|left|200px]]<br /><applet load="1hld" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1hld, resolution 2.1Å" /> | caption="1hld, resolution 2.1Å" /> | ||
'''STRUCTURES OF HORSE LIVER ALCOHOL DEHYDROGENASE COMPLEXED WITH NAD+ AND SUBSTITUTED BENZYL ALCOHOLS'''<br /> | '''STRUCTURES OF HORSE LIVER ALCOHOL DEHYDROGENASE COMPLEXED WITH NAD+ AND SUBSTITUTED BENZYL ALCOHOLS'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Structures of the enzyme complexed with NAD+ and | + | Structures of the enzyme complexed with NAD+ and 2,3,4,5,6-pentafluorobenzyl alcohol were determined by X-ray crystallography at a resolution of 2.1 A and to a refinement R value of 18.3% for a monoclinic (P2(1)) form and to 2.4 A and an R value of 18.9% for a triclinic crystal form. The pentafluorobenzyl alcohol does not react, due to electron withdrawal by the fluorine atoms. A structure with NAD+ and p-bromobenzyl alcohol in the monoclinic form was also determined at 2.5 A and an R value of 16.7%. The conformations of the subunits in the monoclinic and triclinic crystal forms are very similar. The dimer is the asymmetric unit, and a rigid body rotation closes the cleft between the coenzyme and catalytic domains upon complex formation. In the monoclinic form, this conformational change is described by a rotation of 9 degrees in one subunit and 10 degrees in the other. The pentafluoro- and p-bromobenzyl alcohols bind in overlapping positions. The hydroxyl group of each alcohol is ligated to the catalytic zinc and participates in an extensive hydrogen-bonded network that includes the imidazole group of His-51, which can act as a base and shuttle a proton to solvent. The hydroxymethyl carbon of the pentafluorobenzyl alcohol is 3.4 A from C4 of the nicotinamide ring, and the pro-R hydrogen is in a good position for direct transfer to C4. The p-bromobenzyl alcohol may react after small rotations around single bonds of the alcohol. These structures should approximate the active Michaelis-Menten complexes. |
==About this Structure== | ==About this Structure== | ||
| - | 1HLD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Equus_caballus Equus caballus] with ZN, NAD, PFB and BRB 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:// | + | 1HLD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Equus_caballus Equus caballus] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=NAD:'>NAD</scene>, <scene name='pdbligand=PFB:'>PFB</scene> and <scene name='pdbligand=BRB:'>BRB</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=1HLD OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Eklund, H.]] | [[Category: Eklund, H.]] | ||
| - | [[Category: Plapp, B | + | [[Category: Plapp, B V.]] |
[[Category: Ramaswamy, S.]] | [[Category: Ramaswamy, S.]] | ||
[[Category: BRB]] | [[Category: BRB]] | ||
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[[Category: oxidoreductase(ch-oh(d)-nad(a))]] | [[Category: oxidoreductase(ch-oh(d)-nad(a))]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:02:28 2008'' |
Revision as of 11:02, 21 February 2008
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STRUCTURES OF HORSE LIVER ALCOHOL DEHYDROGENASE COMPLEXED WITH NAD+ AND SUBSTITUTED BENZYL ALCOHOLS
Overview
Structures of the enzyme complexed with NAD+ and 2,3,4,5,6-pentafluorobenzyl alcohol were determined by X-ray crystallography at a resolution of 2.1 A and to a refinement R value of 18.3% for a monoclinic (P2(1)) form and to 2.4 A and an R value of 18.9% for a triclinic crystal form. The pentafluorobenzyl alcohol does not react, due to electron withdrawal by the fluorine atoms. A structure with NAD+ and p-bromobenzyl alcohol in the monoclinic form was also determined at 2.5 A and an R value of 16.7%. The conformations of the subunits in the monoclinic and triclinic crystal forms are very similar. The dimer is the asymmetric unit, and a rigid body rotation closes the cleft between the coenzyme and catalytic domains upon complex formation. In the monoclinic form, this conformational change is described by a rotation of 9 degrees in one subunit and 10 degrees in the other. The pentafluoro- and p-bromobenzyl alcohols bind in overlapping positions. The hydroxyl group of each alcohol is ligated to the catalytic zinc and participates in an extensive hydrogen-bonded network that includes the imidazole group of His-51, which can act as a base and shuttle a proton to solvent. The hydroxymethyl carbon of the pentafluorobenzyl alcohol is 3.4 A from C4 of the nicotinamide ring, and the pro-R hydrogen is in a good position for direct transfer to C4. The p-bromobenzyl alcohol may react after small rotations around single bonds of the alcohol. These structures should approximate the active Michaelis-Menten complexes.
About this Structure
1HLD is a Single protein structure of sequence from Equus caballus with , , and as ligands. Active as Alcohol dehydrogenase, with EC number 1.1.1.1 Full crystallographic information is available from OCA.
Reference
Structures of horse liver alcohol dehydrogenase complexed with NAD+ and substituted benzyl alcohols., Ramaswamy S, Eklund H, Plapp BV, Biochemistry. 1994 May 3;33(17):5230-7. PMID:8172897
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