1pn2
From Proteopedia
(New page: 200px<br /><applet load="1pn2" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pn2, resolution 1.95Å" /> '''Crystal structure an...) |
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| - | [[Image:1pn2.jpg|left|200px]]<br /><applet load="1pn2" size=" | + | [[Image:1pn2.jpg|left|200px]]<br /><applet load="1pn2" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1pn2, resolution 1.95Å" /> | caption="1pn2, resolution 1.95Å" /> | ||
'''Crystal structure analysis of the selenomethionine labelled 2-enoyl-CoA hydratase 2 domain of Candida tropicalis multifunctional enzyme type 2'''<br /> | '''Crystal structure analysis of the selenomethionine labelled 2-enoyl-CoA hydratase 2 domain of Candida tropicalis multifunctional enzyme type 2'''<br /> | ||
==Overview== | ==Overview== | ||
| - | 2-Enoyl-CoA hydratase 2, a part from multifunctional enzyme type 2, hydrates trans-2-enoyl-CoA to 3-hydroxyacyl-CoA in the | + | 2-Enoyl-CoA hydratase 2, a part from multifunctional enzyme type 2, hydrates trans-2-enoyl-CoA to 3-hydroxyacyl-CoA in the (3R)-hydroxy-dependent route of peroxisomal beta-oxidation of fatty acids. Unliganded and (3R)-hydroxydecanoyl coenzyme A-complexed crystal structures of 2-enoyl-CoA hydratase 2 from Candida tropicalis multifunctional enzyme type 2 were solved to 1.95- and 2.35-A resolution, respectively. 2-Enoyl-CoA hydratase 2 is a dimeric, alpha+beta protein with a novel quaternary structure. The overall structure of the two-domain subunit of eukaryotic 2-enoyl-CoA hydratase 2 resembles the homodimeric, hot dog fold structures of prokaryotic (R)-specific 2-enoyl-CoA hydratase and beta-hydroxydecanoyl thiol ester dehydrase. Importantly, though, the eukaryotic hydratase 2 has a complete hot dog fold only in its C-domain, whereas the N-domain lacks a long central alpha-helix, thus creating space for bulkier substrates in the binding pocket and explaining the observed difference in substrate preference between eukaryotic and prokaryotic enzymes. Although the N- and C-domains have an identity of <10% at the amino acid level, they share a 50% identity at the nucleotide level and fold similarly. We suggest that a subunit of 2-enoyl-CoA hydratase 2 has evolved via a gene duplication with the concomitant loss of one catalytic site. The hydrogen bonding network of the active site of 2-enoyl-CoA hydratase 2 resembles the active site geometry of mitochondrial (S)-specific 2-enoyl-CoA hydratase 1, although in a mirror image fashion. This arrangement allows the reaction to occur by similar mechanism, supported by mutagenesis and mechanistic studies, although via reciprocal stereochemistry. |
==About this Structure== | ==About this Structure== | ||
| - | 1PN2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Candida_tropicalis Candida tropicalis] with EDO as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1PN2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Candida_tropicalis Candida tropicalis] with <scene name='pdbligand=EDO:'>EDO</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PN2 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Glumoff, T.]] | [[Category: Glumoff, T.]] | ||
| - | [[Category: Haapalainen, A | + | [[Category: Haapalainen, A M.]] |
| - | [[Category: Hiltunen, J | + | [[Category: Hiltunen, J K.]] |
| - | [[Category: Koski, M | + | [[Category: Koski, M K.]] |
[[Category: EDO]] | [[Category: EDO]] | ||
[[Category: hot-dog fold]] | [[Category: hot-dog fold]] | ||
[[Category: hydratase 2 motif]] | [[Category: hydratase 2 motif]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:30:25 2008'' |
Revision as of 12:30, 21 February 2008
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Crystal structure analysis of the selenomethionine labelled 2-enoyl-CoA hydratase 2 domain of Candida tropicalis multifunctional enzyme type 2
Overview
2-Enoyl-CoA hydratase 2, a part from multifunctional enzyme type 2, hydrates trans-2-enoyl-CoA to 3-hydroxyacyl-CoA in the (3R)-hydroxy-dependent route of peroxisomal beta-oxidation of fatty acids. Unliganded and (3R)-hydroxydecanoyl coenzyme A-complexed crystal structures of 2-enoyl-CoA hydratase 2 from Candida tropicalis multifunctional enzyme type 2 were solved to 1.95- and 2.35-A resolution, respectively. 2-Enoyl-CoA hydratase 2 is a dimeric, alpha+beta protein with a novel quaternary structure. The overall structure of the two-domain subunit of eukaryotic 2-enoyl-CoA hydratase 2 resembles the homodimeric, hot dog fold structures of prokaryotic (R)-specific 2-enoyl-CoA hydratase and beta-hydroxydecanoyl thiol ester dehydrase. Importantly, though, the eukaryotic hydratase 2 has a complete hot dog fold only in its C-domain, whereas the N-domain lacks a long central alpha-helix, thus creating space for bulkier substrates in the binding pocket and explaining the observed difference in substrate preference between eukaryotic and prokaryotic enzymes. Although the N- and C-domains have an identity of <10% at the amino acid level, they share a 50% identity at the nucleotide level and fold similarly. We suggest that a subunit of 2-enoyl-CoA hydratase 2 has evolved via a gene duplication with the concomitant loss of one catalytic site. The hydrogen bonding network of the active site of 2-enoyl-CoA hydratase 2 resembles the active site geometry of mitochondrial (S)-specific 2-enoyl-CoA hydratase 1, although in a mirror image fashion. This arrangement allows the reaction to occur by similar mechanism, supported by mutagenesis and mechanistic studies, although via reciprocal stereochemistry.
About this Structure
1PN2 is a Single protein structure of sequence from Candida tropicalis with as ligand. Full crystallographic information is available from OCA.
Reference
A two-domain structure of one subunit explains unique features of eukaryotic hydratase 2., Koski MK, Haapalainen AM, Hiltunen JK, Glumoff T, J Biol Chem. 2004 Jun 4;279(23):24666-72. Epub 2004 Mar 29. PMID:15051722
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