1udy: Difference between revisions
New page: left|200px<br /><applet load="1udy" size="450" color="white" frame="true" align="right" spinBox="true" caption="1udy, resolution 2.4Å" /> '''Medium-Chain Acyl-CoA... |
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[[Image:1udy.jpg|left|200px]]<br /><applet load="1udy" size=" | [[Image:1udy.jpg|left|200px]]<br /><applet load="1udy" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1udy, resolution 2.4Å" /> | caption="1udy, resolution 2.4Å" /> | ||
'''Medium-Chain Acyl-CoA Dehydrogenase with 3-Thiaoctanoyl-CoA'''<br /> | '''Medium-Chain Acyl-CoA Dehydrogenase with 3-Thiaoctanoyl-CoA'''<br /> | ||
==Overview== | ==Overview== | ||
The flavoenzyme medium-chain acyl-CoA dehydrogenase (MCAD) eliminates the | The flavoenzyme medium-chain acyl-CoA dehydrogenase (MCAD) eliminates the alpha-proton of the substrate analog, 3-thiaoctanoyl-CoA (3S-C8-CoA), to form a charge-transfer complex with deprotonated 3S-C8-CoA. This complex can simulate the metastable reaction intermediate immediately after the alpha-proton elimination of a substrate and before the beta-hydrogen transfer as a hydride, and is therefore regarded as a transition-state analog. The crystalline complex was obtained by co-crystallizing MCAD in the oxidized form with 3S-C8-CoA. The three-dimensional structure of the complex was solved by X-ray crystallography. The deprotonated 3S-C8-CoA was clearly located within the active-site cleft of the enzyme. The arrangement between the flavin ring and deprotonated 3S-C8-CoA is consistent with a charge transfer interaction with the negatively charged acyl-chain of 3S-C8-CoA as an electron donor stacking on the pyrimidine moiety of the flavin ring as an electron acceptor. The structure of the model complex between lumiflavin and the deprotonated ethylthioester of 3-thiabutanoic acid was optimized by molecular orbital calculations. The obtained theoretical structure was essentially the same as that of the corresponding region of the X-ray structure. A considerable amount of negative charge is transferred to the flavin ring system to stabilize the complex by 9.2 kcal/mol. The large stabilization energy by charge transfer probably plays an important role in determining the alignment of the flavin ring with 3S-C8-CoA. The structure of the highest occupied molecular orbital of the complex revealed the electron flow pathway from a substrate to the flavin ring. | ||
==About this Structure== | ==About this Structure== | ||
1UDY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with FAD and CS8 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Acyl-CoA_dehydrogenase Acyl-CoA dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.99.3 1.3.99.3] Full crystallographic information is available from [http:// | 1UDY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with <scene name='pdbligand=FAD:'>FAD</scene> and <scene name='pdbligand=CS8:'>CS8</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Acyl-CoA_dehydrogenase Acyl-CoA dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.99.3 1.3.99.3] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UDY OCA]. | ||
==Reference== | ==Reference== | ||
Structure of the transition state analog of medium-chain acyl-CoA dehydrogenase. Crystallographic and molecular orbital studies on the charge-transfer complex of medium-chain acyl-CoA dehydrogenase with 3-thiaoctanoyl-CoA., Satoh A, Nakajima Y, Miyahara I, Hirotsu K, Tanaka T, Nishina Y, Shiga K, Tamaoki H, Setoyama C, Miura R, J Biochem | Structure of the transition state analog of medium-chain acyl-CoA dehydrogenase. Crystallographic and molecular orbital studies on the charge-transfer complex of medium-chain acyl-CoA dehydrogenase with 3-thiaoctanoyl-CoA., Satoh A, Nakajima Y, Miyahara I, Hirotsu K, Tanaka T, Nishina Y, Shiga K, Tamaoki H, Setoyama C, Miura R, J Biochem. 2003 Aug;134(2):297-304. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12966080 12966080] | ||
[[Category: Acyl-CoA dehydrogenase]] | [[Category: Acyl-CoA dehydrogenase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: mcad complex]] | [[Category: mcad complex]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:23:25 2008'' | ||
Revision as of 16:23, 21 February 2008
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Medium-Chain Acyl-CoA Dehydrogenase with 3-Thiaoctanoyl-CoA
OverviewOverview
The flavoenzyme medium-chain acyl-CoA dehydrogenase (MCAD) eliminates the alpha-proton of the substrate analog, 3-thiaoctanoyl-CoA (3S-C8-CoA), to form a charge-transfer complex with deprotonated 3S-C8-CoA. This complex can simulate the metastable reaction intermediate immediately after the alpha-proton elimination of a substrate and before the beta-hydrogen transfer as a hydride, and is therefore regarded as a transition-state analog. The crystalline complex was obtained by co-crystallizing MCAD in the oxidized form with 3S-C8-CoA. The three-dimensional structure of the complex was solved by X-ray crystallography. The deprotonated 3S-C8-CoA was clearly located within the active-site cleft of the enzyme. The arrangement between the flavin ring and deprotonated 3S-C8-CoA is consistent with a charge transfer interaction with the negatively charged acyl-chain of 3S-C8-CoA as an electron donor stacking on the pyrimidine moiety of the flavin ring as an electron acceptor. The structure of the model complex between lumiflavin and the deprotonated ethylthioester of 3-thiabutanoic acid was optimized by molecular orbital calculations. The obtained theoretical structure was essentially the same as that of the corresponding region of the X-ray structure. A considerable amount of negative charge is transferred to the flavin ring system to stabilize the complex by 9.2 kcal/mol. The large stabilization energy by charge transfer probably plays an important role in determining the alignment of the flavin ring with 3S-C8-CoA. The structure of the highest occupied molecular orbital of the complex revealed the electron flow pathway from a substrate to the flavin ring.
About this StructureAbout this Structure
1UDY is a Single protein structure of sequence from Sus scrofa with and as ligands. Active as Acyl-CoA dehydrogenase, with EC number 1.3.99.3 Full crystallographic information is available from OCA.
ReferenceReference
Structure of the transition state analog of medium-chain acyl-CoA dehydrogenase. Crystallographic and molecular orbital studies on the charge-transfer complex of medium-chain acyl-CoA dehydrogenase with 3-thiaoctanoyl-CoA., Satoh A, Nakajima Y, Miyahara I, Hirotsu K, Tanaka T, Nishina Y, Shiga K, Tamaoki H, Setoyama C, Miura R, J Biochem. 2003 Aug;134(2):297-304. PMID:12966080
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