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==Three dimensional structure of human gamma-butyrobetaine hydroxylase in complex with 3-Carboxy-N-(2-fluoroethyl)-N,N-dimethylpropan-1- aminium chloride== | ==Three dimensional structure of human gamma-butyrobetaine hydroxylase in complex with 3-Carboxy-N-(2-fluoroethyl)-N,N-dimethylpropan-1- aminium chloride== | ||
<StructureSection load='4bgm' size='340' side='right' caption='[[4bgm]], [[Resolution|resolution]] 2.40Å' scene=''> | <StructureSection load='4bgm' size='340' side='right'caption='[[4bgm]], [[Resolution|resolution]] 2.40Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4bgm]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4bgm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BGM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BGM FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=16D:HEXANE-1,6-DIAMINE'>16D</scene>, <scene name='pdbligand=DLT:3-CARBOXY-N-(2-FLUOROETHYL)-N,N-DIMETHYLPROPAN-1-AMINIUM'>DLT</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=16D:HEXANE-1,6-DIAMINE'>16D</scene>, <scene name='pdbligand=DLT:3-CARBOXY-N-(2-FLUOROETHYL)-N,N-DIMETHYLPROPAN-1-AMINIUM'>DLT</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4bgm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bgm OCA], [https://pdbe.org/4bgm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bgm RCSB], [https://www.ebi.ac.uk/pdbsum/4bgm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bgm ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/BODG_HUMAN BODG_HUMAN] Catalyzes the formation of L-carnitine from gamma-butyrobetaine. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 20: | Line 19: | ||
</div> | </div> | ||
<div class="pdbe-citations 4bgm" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 4bgm" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Dioxygenase 3D structures|Dioxygenase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Kazaks | [[Category: Kazaks A]] | ||
[[Category: Leitans | [[Category: Leitans J]] | ||
[[Category: Tars | [[Category: Tars K]] | ||
Latest revision as of 14:51, 20 December 2023
Three dimensional structure of human gamma-butyrobetaine hydroxylase in complex with 3-Carboxy-N-(2-fluoroethyl)-N,N-dimethylpropan-1- aminium chlorideThree dimensional structure of human gamma-butyrobetaine hydroxylase in complex with 3-Carboxy-N-(2-fluoroethyl)-N,N-dimethylpropan-1- aminium chloride
Structural highlights
FunctionBODG_HUMAN Catalyzes the formation of L-carnitine from gamma-butyrobetaine. Publication Abstract from PubMedGamma butyrobetaine hydroxylase (BBOX) catalyzes the conversion of gamma butyrobetaine (GBB) to L-carnitine, which is involved in the generation of metabolic energy from long chain fatty acids. BBOX inhibitor 3-(1,1,1-trimethylhydrazin-1-ium-2-yl)propanoate (mildronate), which is an approved, clinically used cardioprotective drug, is a relatively poor BBOX inhibitor and requires high daily doses. In this disclosure, we describe the design, synthesis and properties of 51 compounds, which include both GBB and mildronate analogues. We have discovered novel BBOX inhibitors with improved IC50 values; the best examples are in nanomolar range and about two orders of magnitude better when compared to mildronate. For 6 inhibitors, crystal structures in complex with BBOX have been solved to explain their activities and pave way for further inhibitor design. Targeting carnitine biosynthesis: discovery of new inhibitors against gamma-butyrobetaine hydroxylase.,Tars K, Leitans J, Kazaks A, Zelencova D, Liepinsh E, Kuka J, Makrecka M, Lola D, Andrianovs V, Gustina D, Grinberga S, Liepinsh E, Kalvinsh I, Dambrova M, Loza E, Pugovics O J Med Chem. 2014 Feb 26. PMID:24571165[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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