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6rq8
From Proteopedia
(Difference between revisions)
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==CYP121 in complex with 3-iodo dicyclotyrosine== | ==CYP121 in complex with 3-iodo dicyclotyrosine== | ||
| - | <StructureSection load='6rq8' size='340' side='right'caption='[[6rq8]]' scene=''> | + | <StructureSection load='6rq8' size='340' side='right'caption='[[6rq8]], [[Resolution|resolution]] 1.41Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RQ8 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6RQ8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6rq8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RQ8 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6RQ8 FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6rq8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rq8 OCA], [http://pdbe.org/6rq8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rq8 RCSB], [http://www.ebi.ac.uk/pdbsum/6rq8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rq8 ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=KEH:(3~{S},6~{S})-3-[(4-hydroxyphenyl)methyl]-6-[(3-iodanyl-4-oxidanyl-phenyl)methyl]piperazine-2,5-dione'>KEH</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">cyp121, MT2336 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Oxidoreductase Oxidoreductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.19.70 1.14.19.70] </span></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6rq8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rq8 OCA], [http://pdbe.org/6rq8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rq8 RCSB], [http://www.ebi.ac.uk/pdbsum/6rq8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rq8 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/CP121_MYCTO CP121_MYCTO]] Catalyzes C-C bond formation between the carbons ortho to the phenolic hydroxyl of cyclo(L-tyr-L-tyr) (cYY) producing mycocyclosin. Can also use cyclo(L-Tyr-L-Phe) (cYF), cyclo(L-Tyr-L-Trp) (cYW) and cyclo(L-Tyr-L-3,4-dihydroxyphenylalanine) (cY-DOPA) as substrate (By similarity). | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | A series of analogues of cyclo(l-tyrosyl-l-tyrosine), the substrate of the Mycobacterium tuberculosis enzyme CYP121, have been synthesized and analyzed by UV-vis and electron paramagnetic resonance spectroscopy and by X-ray crystallography. The introduction of iodine substituents onto cyclo(l-tyrosyl-l-tyrosine) results in sub-muM binding affinity for the CYP121 enzyme and a complete shift to the high-spin state of the heme Fe(III). The introduction of halogens that are able to interact with heme groups is thus a feasible approach to the development of next-generation, tight binding inhibitors of the CYP121 enzyme, in the search for novel antitubercular compounds. | ||
| + | |||
| + | Structure-Activity Relationships of cyclo(l-Tyrosyl-l-tyrosine) Derivatives Binding to Mycobacterium tuberculosis CYP121: Iodinated Analogues Promote Shift to High-Spin Adduct.,Rajput S, McLean KJ, Poddar H, Selvam IR, Nagalingam G, Triccas JA, Levy CW, Munro AW, Hutton CA J Med Chem. 2019 Nov 14;62(21):9792-9805. doi: 10.1021/acs.jmedchem.9b01199. Epub, 2019 Oct 31. PMID:31618032<ref>PMID:31618032</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6rq8" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Levy C]] | + | [[Category: Oxidoreductase]] |
| - | [[Category: Poddar H]] | + | [[Category: Levy, C]] |
| + | [[Category: Poddar, H]] | ||
| + | [[Category: Cyp121]] | ||
| + | [[Category: Dicyclotyrosine derivative]] | ||
| + | [[Category: Heme]] | ||
| + | [[Category: P450]] | ||
Revision as of 09:49, 18 November 2020
CYP121 in complex with 3-iodo dicyclotyrosine
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