3ms5

<table><tr><td colspan='2'>[[3ms5]] 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=3MS5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3MS5 FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</scene>, <scene name='pdbligand=REE:2-(2-CARBOXYETHYL)-1,1,1-TRIMETHYLDIAZANIUM'>REE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Gamma-butyrobetaine_dioxygenase Gamma-butyrobetaine dioxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.11.1 1.14.11.1] </span></td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ms5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ms5 OCA], [http://pdbe.org/3ms5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ms5 RCSB], [http://www.ebi.ac.uk/pdbsum/3ms5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ms5 ProSAT]</span></td></tr>

[[http://www.uniprot.org/uniprot/BODG_HUMAN BODG_HUMAN]] Catalyzes the formation of L-carnitine from gamma-butyrobetaine.

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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.

 

== References ==

[[Category: Gamma-butyrobetaine dioxygenase]]

[[Category: Human]]

[[Category: Arrowsmith, C H]]

[[Category: Bountra, C]]

[[Category: Claridge, T D.W]]

[[Category: Delft, F von]]

[[Category: Edwards, A]]

[[Category: Filippakopoulos, P]]

[[Category: Henry, L]]

[[Category: Kavanagh, K L]]

[[Category: Kochan, G]]

[[Category: Krojer, T]]

[[Category: Leung, I K.H]]

[[Category: McDonough, M A]]

[[Category: Muniz, J]]

[[Category: Oppermann, U]]

[[Category: Pilka, E]]

[[Category: Structural genomic]]

[[Category: Schofield, C J]]

[[Category: Ugochukwu, E]]

[[Category: Weigelt, J]]

[[Category: 2-oxoglutarate dioxygenase 1]]

[[Category: Sgc]]