2bfd: Difference between revisions
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[[Image:2bfd.gif|left|200px]]<br /> | [[Image:2bfd.gif|left|200px]]<br /><applet load="2bfd" size="450" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="2bfd" size="450" color="white" frame="true" align="right" spinBox="true" | |||
caption="2bfd, resolution 1.39Å" /> | caption="2bfd, resolution 1.39Å" /> | ||
'''REACTIVITY MODULATION OF HUMAN BRANCHED-CHAIN ALPHA-KETOACID DEHYDROGENASE BY AN INTERNAL MOLECULAR SWITCH'''<br /> | '''REACTIVITY MODULATION OF HUMAN BRANCHED-CHAIN ALPHA-KETOACID DEHYDROGENASE BY AN INTERNAL MOLECULAR SWITCH'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
2BFD is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with K, MN, CL, TDP, GOL and MPD as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/3-methyl-2-oxobutanoate_dehydrogenase_(2-methylpropanoyl-transferring) 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.4.4 1.2.4.4] | 2BFD is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with K, MN, CL, TDP, GOL and MPD as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/3-methyl-2-oxobutanoate_dehydrogenase_(2-methylpropanoyl-transferring) 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.4.4 1.2.4.4] Known structural/functional Site: <scene name='pdbsite=AC1:Mpd Binding Site For Chain B'>AC1</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BFD OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: thiamine diphosphate]] | [[Category: thiamine diphosphate]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 18:45:02 2007'' | ||
Revision as of 19:35, 18 December 2007
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REACTIVITY MODULATION OF HUMAN BRANCHED-CHAIN ALPHA-KETOACID DEHYDROGENASE BY AN INTERNAL MOLECULAR SWITCH
OverviewOverview
The dehydrogenase/decarboxylase (E1b) component of the 4 MD human, branched-chain alpha-ketoacid dehydrogenase complex (BCKDC) is a thiamin, diphosphate (ThDP)-dependent enzyme. We have determined the crystal, structures of E1b with ThDP bound intermediates after decarboxylation of, alpha-ketoacids. We show that a key tyrosine residue in the E1b active, site functions as a conformational switch to reduce the reactivity of the, ThDP cofactor through interactions with its thiazolium ring. The, intermediates do not assume the often-postulated enamine state, but likely, a carbanion state. The carbanion presumably facilitates the second, E1b-catalyzed reaction, involving the transfer of an acyl moiety from the, intermediate to a lipoic acid prosthetic group in the transacylase (E2b), component of the BCKDC. The tyrosine switch further remodels an E1b loop, region to promote E1b binding to E2b. Our results illustrate the, versatility of the tyrosine switch in coordinating the catalytic events in, E1b by modulating the reactivity of reaction intermediates.
DiseaseDisease
Known diseases associated with this structure: Maple syrup urine disease, type Ia OMIM:[608348], Maple syrup urine disease, type Ib OMIM:[248611]
About this StructureAbout this Structure
2BFD is a Protein complex structure of sequences from Homo sapiens with K, MN, CL, TDP, GOL and MPD as ligands. Active as 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring), with EC number 1.2.4.4 Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
A versatile conformational switch regulates reactivity in human branched-chain alpha-ketoacid dehydrogenase., Machius M, Wynn RM, Chuang JL, Li J, Kluger R, Yu D, Tomchick DR, Brautigam CA, Chuang DT, Structure. 2006 Feb;14(2):287-98. PMID:16472748
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OCA- Pages with broken file links
- 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring)
- Homo sapiens
- Protein complex
- Brautigam, C.A.
- Chuang, D.T.
- Chuang, J.L.
- Machius, M.
- Tomchick, D.R.
- Wynn, R.M.
- CL
- GOL
- K
- MN
- MPD
- TDP
- Acylation
- Branched-chain
- Conformational switch
- Ketoacid dehydrogenase
- Maple syrup urine disease
- Multi-enzyme complex
- Oxidative decarboxylation
- Oxidoreductase
- Phosphorylation
- Reactivity
- Thiamine diphosphate