1xlt
From Proteopedia
(New page: 200px<br /><applet load="1xlt" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xlt, resolution 3.10Å" /> '''Crystal structure of...) |
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| - | [[Image:1xlt.gif|left|200px]]<br /><applet load="1xlt" size=" | + | [[Image:1xlt.gif|left|200px]]<br /><applet load="1xlt" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1xlt, resolution 3.10Å" /> | caption="1xlt, resolution 3.10Å" /> | ||
'''Crystal structure of Transhydrogenase [(domain I)2:domain III] heterotrimer complex'''<br /> | '''Crystal structure of Transhydrogenase [(domain I)2:domain III] heterotrimer complex'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Transhydrogenase (TH) couples direct and stereospecific hydride transfer | + | Transhydrogenase (TH) couples direct and stereospecific hydride transfer between NAD(H) and NADP(H), bound within soluble domains I and III, respectively, to proton translocation across membrane bound domain II. The cocrystal structure of Rhodospirillum rubrum TH domains I and III has been determined in the presence of limiting NADH, under conditions in which the subunits reach equilibrium during crystallization. The crystals contain three heterotrimeric complexes, dI(2)dIII, in the asymmetric unit. Multiple conformations of loops and side-chains, and NAD(H) cofactors, are observed in domain I pertaining to substrate/product exchange, and highlighting electrostatic interactions during the hydride transfer. Two interacting NAD(H)-NADPH pairs are observed where alternate conformations of the NAD(H) phosphodiester and conserved arginine side-chains are correlated. In addition, the stereochemistry of one NAD(H)-NADPH pair approaches that expected for nicotinamide hydride transfer reactions. The cocrystal structure exhibits non-crystallographic symmetry that implies another orientation for domain III, which could occur in dimeric TH. Superposition of the "closed" form of domain III (PDB 1PNO, chain A) onto the dI(2)dIII complex reveals a severe steric conflict of highly conserved loops in domains I and III. This overlap, and the overlap with a 2-fold related domain III, suggests that motions of loop D within domain III and of the entire domain are correlated during turnover. The results support the concept that proton pumping in TH is driven by the difference in binding affinity for oxidized and reduced nicotinamide cofactors, and in the absence of a difference in redox potential, must occur through conformational effects. |
==About this Structure== | ==About this Structure== | ||
| - | 1XLT is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Rhodospirillum_rubrum Rhodospirillum rubrum] with SUC, NA, NAD and NDP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/NAD(P)(+)_transhydrogenase_(AB-specific) NAD(P)(+) transhydrogenase (AB-specific)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.6.1.2 1.6.1.2] Full crystallographic information is available from [http:// | + | 1XLT is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Rhodospirillum_rubrum Rhodospirillum rubrum] with <scene name='pdbligand=SUC:'>SUC</scene>, <scene name='pdbligand=NA:'>NA</scene>, <scene name='pdbligand=NAD:'>NAD</scene> and <scene name='pdbligand=NDP:'>NDP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/NAD(P)(+)_transhydrogenase_(AB-specific) NAD(P)(+) transhydrogenase (AB-specific)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.6.1.2 1.6.1.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XLT OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Rhodospirillum rubrum]] | [[Category: Rhodospirillum rubrum]] | ||
[[Category: Chartron, J.]] | [[Category: Chartron, J.]] | ||
| - | [[Category: Stout, C | + | [[Category: Stout, C D.]] |
[[Category: Sundaresan, V.]] | [[Category: Sundaresan, V.]] | ||
[[Category: Yamaguchi, M.]] | [[Category: Yamaguchi, M.]] | ||
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[[Category: transhydrogenase]] | [[Category: transhydrogenase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:56:13 2008'' |
Revision as of 13:56, 21 February 2008
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Crystal structure of Transhydrogenase [(domain I)2:domain III] heterotrimer complex
Overview
Transhydrogenase (TH) couples direct and stereospecific hydride transfer between NAD(H) and NADP(H), bound within soluble domains I and III, respectively, to proton translocation across membrane bound domain II. The cocrystal structure of Rhodospirillum rubrum TH domains I and III has been determined in the presence of limiting NADH, under conditions in which the subunits reach equilibrium during crystallization. The crystals contain three heterotrimeric complexes, dI(2)dIII, in the asymmetric unit. Multiple conformations of loops and side-chains, and NAD(H) cofactors, are observed in domain I pertaining to substrate/product exchange, and highlighting electrostatic interactions during the hydride transfer. Two interacting NAD(H)-NADPH pairs are observed where alternate conformations of the NAD(H) phosphodiester and conserved arginine side-chains are correlated. In addition, the stereochemistry of one NAD(H)-NADPH pair approaches that expected for nicotinamide hydride transfer reactions. The cocrystal structure exhibits non-crystallographic symmetry that implies another orientation for domain III, which could occur in dimeric TH. Superposition of the "closed" form of domain III (PDB 1PNO, chain A) onto the dI(2)dIII complex reveals a severe steric conflict of highly conserved loops in domains I and III. This overlap, and the overlap with a 2-fold related domain III, suggests that motions of loop D within domain III and of the entire domain are correlated during turnover. The results support the concept that proton pumping in TH is driven by the difference in binding affinity for oxidized and reduced nicotinamide cofactors, and in the absence of a difference in redox potential, must occur through conformational effects.
About this Structure
1XLT is a Protein complex structure of sequences from Rhodospirillum rubrum with , , and as ligands. Active as NAD(P)(+) transhydrogenase (AB-specific), with EC number 1.6.1.2 Full crystallographic information is available from OCA.
Reference
Conformational diversity in NAD(H) and interacting transhydrogenase nicotinamide nucleotide binding domains., Sundaresan V, Chartron J, Yamaguchi M, Stout CD, J Mol Biol. 2005 Feb 18;346(2):617-29. Epub 2004 Dec 30. PMID:15670609
Page seeded by OCA on Thu Feb 21 15:56:13 2008
Categories: NAD(P)(+) transhydrogenase (AB-specific) | Protein complex | Rhodospirillum rubrum | Chartron, J. | Stout, C D. | Sundaresan, V. | Yamaguchi, M. | NA | NAD | NDP | SUC | Nad | Nadh | Nadp | Nadph | Transhydrogenase
