1ivh
From Proteopedia
(New page: 200px<br /> <applet load="1ivh" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ivh, resolution 2.60Å" /> '''STRUCTURE OF HUMAN ...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1ivh.gif|left|200px]]<br /> | + | [[Image:1ivh.gif|left|200px]]<br /><applet load="1ivh" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1ivh" size=" | + | |
caption="1ivh, resolution 2.60Å" /> | caption="1ivh, resolution 2.60Å" /> | ||
'''STRUCTURE OF HUMAN ISOVALERYL-COA DEHYDROGENASE AT 2.6 ANGSTROMS RESOLUTION: STRUCTURAL BASIS FOR SUBSTRATE SPECIFICITY'''<br /> | '''STRUCTURE OF HUMAN ISOVALERYL-COA DEHYDROGENASE AT 2.6 ANGSTROMS RESOLUTION: STRUCTURAL BASIS FOR SUBSTRATE SPECIFICITY'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Isovaleryl-CoA dehydrogenase (IVD) belongs to an important flavoprotein | + | Isovaleryl-CoA dehydrogenase (IVD) belongs to an important flavoprotein family of acyl-CoA dehydrogenases that catalyze the alpha,beta-dehydrogenation of their various thioester substrates. Although enzymes from this family share similar sequences, catalytic mechanisms, and structural properties, the position of the catalytic base in the primary sequence is not conserved. E376 has been confirmed to be the catalytic base in medium-chain (MCAD) and short-chain acyl-CoA dehydrogenases and is conserved in all members of the acyl-CoA dehydrogenase family except for IVD and long-chain acyl-CoA dehydrogenase. To understand this dichotomy and to gain a better understanding of the factors important in determining substrate specificity in this enzyme family, the three-dimensional structure of human IVD has been determined. Human IVD expressed in Escherichia coli crystallizes in the orthorhombic space group P212121 with unit cell parameters a = 94.0 A, b = 97.7 A, and c = 181.7 A. The structure of IVD was solved at 2.6 A resolution by the molecular replacement method and was refined to an R-factor of 20.7% with an Rfree of 28.8%. The overall polypeptide fold of IVD is similar to that of other members of this family for which structural data are available. The tightly bound ligand found in the active site of the structure of IVD is consistent with that of CoA persulfide. The identity of the catalytic base was confirmed to be E254, in agreement with previous molecular modeling and mutagenesis studies. The location of the catalytic residue together with a glycine at position 374, which is a tyrosine in all other members of the acyl-CoA dehydrogenase family, is important for conferring branched-chain substrate specificity to IVD. |
==Disease== | ==Disease== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1IVH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with FAD and COS as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Isovaleryl-CoA_dehydrogenase Isovaleryl-CoA dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.99.10 1.3.99.10] Full crystallographic information is available from [http:// | + | 1IVH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=FAD:'>FAD</scene> and <scene name='pdbligand=COS:'>COS</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Isovaleryl-CoA_dehydrogenase Isovaleryl-CoA dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.99.10 1.3.99.10] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IVH OCA]. |
==Reference== | ==Reference== | ||
| Line 18: | Line 17: | ||
[[Category: Isovaleryl-CoA dehydrogenase]] | [[Category: Isovaleryl-CoA dehydrogenase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Kim, J | + | [[Category: Kim, J J.P.]] |
| - | [[Category: Mohsen, A | + | [[Category: Mohsen, A W.A.]] |
[[Category: Paschke, R.]] | [[Category: Paschke, R.]] | ||
| - | [[Category: Roberts, D | + | [[Category: Roberts, D L.]] |
| - | [[Category: Tiffany, K | + | [[Category: Tiffany, K A.]] |
[[Category: Vockley, J.]] | [[Category: Vockley, J.]] | ||
[[Category: Wang, M.]] | [[Category: Wang, M.]] | ||
| Line 33: | Line 32: | ||
[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:16:03 2008'' |
Revision as of 11:16, 21 February 2008
|
STRUCTURE OF HUMAN ISOVALERYL-COA DEHYDROGENASE AT 2.6 ANGSTROMS RESOLUTION: STRUCTURAL BASIS FOR SUBSTRATE SPECIFICITY
Contents |
Overview
Isovaleryl-CoA dehydrogenase (IVD) belongs to an important flavoprotein family of acyl-CoA dehydrogenases that catalyze the alpha,beta-dehydrogenation of their various thioester substrates. Although enzymes from this family share similar sequences, catalytic mechanisms, and structural properties, the position of the catalytic base in the primary sequence is not conserved. E376 has been confirmed to be the catalytic base in medium-chain (MCAD) and short-chain acyl-CoA dehydrogenases and is conserved in all members of the acyl-CoA dehydrogenase family except for IVD and long-chain acyl-CoA dehydrogenase. To understand this dichotomy and to gain a better understanding of the factors important in determining substrate specificity in this enzyme family, the three-dimensional structure of human IVD has been determined. Human IVD expressed in Escherichia coli crystallizes in the orthorhombic space group P212121 with unit cell parameters a = 94.0 A, b = 97.7 A, and c = 181.7 A. The structure of IVD was solved at 2.6 A resolution by the molecular replacement method and was refined to an R-factor of 20.7% with an Rfree of 28.8%. The overall polypeptide fold of IVD is similar to that of other members of this family for which structural data are available. The tightly bound ligand found in the active site of the structure of IVD is consistent with that of CoA persulfide. The identity of the catalytic base was confirmed to be E254, in agreement with previous molecular modeling and mutagenesis studies. The location of the catalytic residue together with a glycine at position 374, which is a tyrosine in all other members of the acyl-CoA dehydrogenase family, is important for conferring branched-chain substrate specificity to IVD.
Disease
Known disease associated with this structure: Isovaleric acidemia OMIM:[607036]
About this Structure
1IVH is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Isovaleryl-CoA dehydrogenase, with EC number 1.3.99.10 Full crystallographic information is available from OCA.
Reference
Structure of human isovaleryl-CoA dehydrogenase at 2.6 A resolution: structural basis for substrate specificity,., Tiffany KA, Roberts DL, Wang M, Paschke R, Mohsen AW, Vockley J, Kim JJ, Biochemistry. 1997 Jul 15;36(28):8455-64. PMID:9214289
Page seeded by OCA on Thu Feb 21 13:16:03 2008
