3o2g: Difference between revisions
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==Crystal Structure of Human gamma-butyrobetaine,2-oxoglutarate dioxygenase 1 (BBOX1)== | ==Crystal Structure of Human gamma-butyrobetaine,2-oxoglutarate dioxygenase 1 (BBOX1)== | ||
<StructureSection load='3o2g' size='340' side='right' caption='[[3o2g]], [[Resolution|resolution]] 1.78Å' scene=''> | <StructureSection load='3o2g' size='340' side='right'caption='[[3o2g]], [[Resolution|resolution]] 1.78Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3o2g]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O2G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3O2G FirstGlance]. <br> | <table><tr><td colspan='2'>[[3o2g]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O2G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3O2G FirstGlance]. <br> | ||
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3o2g ConSurf]. | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3o2g ConSurf]. | ||
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== Publication Abstract from PubMed == | |||
The final step in carnitine biosynthesis is catalyzed by gamma-butyrobetaine (gammaBB) hydroxylase (BBOX), an iron/2-oxoglutarate (2OG) dependent oxygenase. BBOX is inhibited by trimethylhydrazine-propionate (THP), a clinically used compound. We report structural and mechanistic studies on BBOX and its reaction with THP. Crystallographic and sequence analyses reveal that BBOX and trimethyllysine hydroxylase form a subfamily of 2OG oxygenases that dimerize using an N-terminal domain. The crystal structure reveals the active site is enclosed and how THP competes with gammaBB. THP is a substrate giving formaldehyde (supporting structural links with histone demethylases), dimethylamine, malonic acid semi-aldehyde, and an unexpected product with an additional carbon-carbon bond resulting from N-demethylation coupled to oxidative rearrangement, likely via an unusual radical mechanism. The results provide a basis for development of improved BBOX inhibitors and may inspire the discovery of additional rearrangement reactions. | |||
Structural and mechanistic studies on gamma-butyrobetaine hydroxylase.,Leung IK, Krojer TJ, Kochan GT, Henry L, von Delft F, Claridge TD, Oppermann U, McDonough MA, Schofield CJ Chem Biol. 2010 Dec 22;17(12):1316-24. PMID:21168767<ref>PMID:21168767</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
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<div class="pdbe-citations 3o2g" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Gamma-butyrobetaine dioxygenase]] | [[Category: Gamma-butyrobetaine dioxygenase]] | ||
[[Category: Human]] | [[Category: Human]] | ||
[[Category: Large Structures]] | |||
[[Category: Arrowsmith, C H]] | [[Category: Arrowsmith, C H]] | ||
[[Category: Bountra, C]] | [[Category: Bountra, C]] | ||
