3ben
From Proteopedia
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| - | [[Image:3ben.png|left|200px]] | ||
| - | + | ==Structure of N-(12-imidazolyl-dodecanoyl)-L-leucine inhibitor bound to the heme domain of Cytochrome P450-BM3== | |
| + | <StructureSection load='3ben' size='340' side='right'caption='[[3ben]], [[Resolution|resolution]] 1.65Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3ben]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Priestia_megaterium Priestia megaterium]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BEN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BEN FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.65Å</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=LEH:N-[12-(1H-IMIDAZOL-1-YL)DODECANOYL]-L-LEUCINE'>LEH</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=3ben FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ben OCA], [https://pdbe.org/3ben PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ben RCSB], [https://www.ebi.ac.uk/pdbsum/3ben PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ben ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/CPXB_PRIM2 CPXB_PRIM2] Functions as a fatty acid monooxygenase (PubMed:3106359, PubMed:1727637, PubMed:16566047, PubMed:7578081, PubMed:11695892, PubMed:14653735, PubMed:16403573, PubMed:18004886, PubMed:17077084, PubMed:17868686, PubMed:18298086, PubMed:18619466, PubMed:18721129, PubMed:19492389, PubMed:20180779, PubMed:21110374, PubMed:21875028). Catalyzes hydroxylation of fatty acids at omega-1, omega-2 and omega-3 positions (PubMed:1727637, PubMed:21875028). Shows activity toward medium and long-chain fatty acids, with optimum chain lengths of 12, 14 and 16 carbons (lauric, myristic, and palmitic acids). Able to metabolize some of these primary metabolites to secondary and tertiary products (PubMed:1727637). Marginal activity towards short chain lengths of 8-10 carbons (PubMed:1727637, PubMed:18619466). Hydroxylates highly branched fatty acids, which play an essential role in membrane fluidity regulation (PubMed:16566047). Also displays a NADPH-dependent reductase activity in the C-terminal domain, which allows electron transfer from NADPH to the heme iron of the cytochrome P450 N-terminal domain (PubMed:3106359, PubMed:1727637, PubMed:16566047, PubMed:7578081, PubMed:11695892, PubMed:14653735, PubMed:16403573, PubMed:18004886, PubMed:17077084, PubMed:17868686, PubMed:18298086, PubMed:18619466, PubMed:18721129, PubMed:19492389, PubMed:20180779, PubMed:21110374, PubMed:21875028). Involved in inactivation of quorum sensing signals of other competing bacteria by oxidazing efficiently acyl homoserine lactones (AHLs), molecules involved in quorum sensing signaling pathways, and their lactonolysis products acyl homoserines (AHs) (PubMed:18020460).<ref>PMID:11695892</ref> <ref>PMID:14653735</ref> <ref>PMID:16403573</ref> <ref>PMID:16566047</ref> <ref>PMID:17077084</ref> <ref>PMID:1727637</ref> <ref>PMID:17868686</ref> <ref>PMID:18004886</ref> <ref>PMID:18020460</ref> <ref>PMID:18298086</ref> <ref>PMID:18619466</ref> <ref>PMID:18721129</ref> <ref>PMID:19492389</ref> <ref>PMID:20180779</ref> <ref>PMID:21110374</ref> <ref>PMID:21875028</ref> <ref>PMID:3106359</ref> <ref>PMID:7578081</ref> | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/be/3ben_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </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=3ben ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | P450BM-3 is an extensively studied P450 cytochrome that is naturally fused to a cytochrome P450 reductase domain. Crystal structures of the heme domain of this enzyme have previously generated many insights into features of P450 structure, substrate binding specificity, and conformational changes that occur on substrate binding. Although many P450s are inhibited by imidazole, this compound does not effectively inhibit P450BM-3. Omega-imidazolyl fatty acids have previously been found to be weak inhibitors of the enzyme and show some unusual cooperativity with the substrate lauric acid. We set out to improve the properties of these inhibitors by attaching the omega-imidazolyl fatty acid to the nitrogen of an amino acid group, a tactic that we used previously to increase the potency of substrates. The resulting inhibitors were significantly more potent than their parent compounds lacking the amino acid group. A crystal structure of one of the new inhibitors bound to the heme domain of P450BM-3 reveals that the mode of interaction of the amino acid group with the enzyme is different from that previously observed for acyl amino acid substrates. Further, required movements of residues in the active site to accommodate the imidazole group provide an explanation for the low affinity of imidazole itself. Finally, the previously observed cooperativity with lauric acid is explained by a surprisingly open substrate-access channel lined with hydrophobic residues that could potentially accommodate lauric acid in addition to the inhibitor itself. | ||
| - | + | Crystal structure of inhibitor-bound P450BM-3 reveals open conformation of substrate access channel.,Haines DC, Chen B, Tomchick DR, Bondlela M, Hegde A, Machius M, Peterson JA Biochemistry. 2008 Mar 25;47(12):3662-70. Epub 2008 Feb 26. PMID:18298086<ref>PMID:18298086</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 3ben" style="background-color:#fffaf0;"></div> | |
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==See Also== | ==See Also== | ||
| - | *[[Cytochrome P450|Cytochrome P450]] | + | *[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]] |
| - | + | == References == | |
| - | + | <references/> | |
| - | + | __TOC__ | |
| - | == | + | </StructureSection> |
| - | < | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Priestia megaterium]] |
| - | [[Category: | + | [[Category: Tomchick DR]] |
| - | [[Category: Tomchick | + | |
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Current revision
Structure of N-(12-imidazolyl-dodecanoyl)-L-leucine inhibitor bound to the heme domain of Cytochrome P450-BM3
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