4bhf: Difference between revisions
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==Three dimensional structure of human gamma-butyrobetaine hydroxylase in complex with 4-(Trimethylammonio)pentanoate== | ==Three dimensional structure of human gamma-butyrobetaine hydroxylase in complex with 4-(Trimethylammonio)pentanoate== | ||
<StructureSection load='4bhf' size='340' side='right' caption='[[4bhf]], [[Resolution|resolution]] 2.05Å' scene=''> | <StructureSection load='4bhf' size='340' side='right' caption='[[4bhf]], [[Resolution|resolution]] 2.05Å' scene=''> | ||
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4bg1|4bg1]], [[4bgk|4bgk]], [[4bgm|4bgm]], [[4bhi|4bhi]], [[4c5w|4c5w]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4bg1|4bg1]], [[4bgk|4bgk]], [[4bgm|4bgm]], [[4bhi|4bhi]], [[4c5w|4c5w]]</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='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=4bhf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bhf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bhf RCSB], [http://www.ebi.ac.uk/pdbsum/4bhf PDBsum]</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=4bhf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bhf OCA], [http://pdbe.org/4bhf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4bhf RCSB], [http://www.ebi.ac.uk/pdbsum/4bhf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4bhf ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4bhf" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 00:31, 5 August 2016
Three dimensional structure of human gamma-butyrobetaine hydroxylase in complex with 4-(Trimethylammonio)pentanoateThree dimensional structure of human gamma-butyrobetaine hydroxylase in complex with 4-(Trimethylammonio)pentanoate
Structural highlights
Function[BODG_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. References
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