|
|
| (One intermediate revision not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Chromopyrrolic acid-soaked RebC-10x with bound 7-carboxy-K252c== | | ==Chromopyrrolic acid-soaked RebC-10x with bound 7-carboxy-K252c== |
| - | <StructureSection load='4eiq' size='340' side='right' caption='[[4eiq]], [[Resolution|resolution]] 2.76Å' scene=''> | + | <StructureSection load='4eiq' size='340' side='right'caption='[[4eiq]], [[Resolution|resolution]] 2.76Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4eiq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"nocardia_aerocolonigenes"_(shinobu_and_kawato_1960)_pridham_1970 "nocardia aerocolonigenes" (shinobu and kawato 1960) pridham 1970]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EIQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EIQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4eiq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Lentzea_aerocolonigenes Lentzea aerocolonigenes]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EIQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EIQ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=KCT:(5S)-7-OXO-6,7,12,13-TETRAHYDRO-5H-INDOLO[2,3-A]PYRROLO[3,4-C]CARBAZOLE-5-CARBOXYLIC+ACID'>KCT</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.76Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2r0g|2r0g]], [[4eip|4eip]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KCT:(5S)-7-OXO-6,7,12,13-TETRAHYDRO-5H-INDOLO[2,3-A]PYRROLO[3,4-C]CARBAZOLE-5-CARBOXYLIC+ACID'>KCT</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">rbmD, rebC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=68170 "Nocardia aerocolonigenes" (Shinobu and Kawato 1960) Pridham 1970])</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=4eiq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eiq OCA], [https://pdbe.org/4eiq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eiq RCSB], [https://www.ebi.ac.uk/pdbsum/4eiq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eiq ProSAT]</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=4eiq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eiq OCA], [http://pdbe.org/4eiq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4eiq RCSB], [http://www.ebi.ac.uk/pdbsum/4eiq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4eiq ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/Q8KI25_LENAE Q8KI25_LENAE] |
| - | The indolocarbazole biosynthetic enzymes StaC, InkE, RebC, and AtmC mediate the degree of oxidation of chromopyrrolic acid on route to the natural products staurosporine, K252a, rebeccamycin, and AT2433-A1, respectively. Here, we show that StaC and InkE, which mediate a net 4-electron oxidation, bind FAD with a micromolar K(d), whereas RebC and AtmC, which mediate a net 8-electron oxidation, bind FAD with a nanomolar K(d) while displaying the same FAD redox properties. We further create RebC-10x, a RebC protein with ten StaC-like amino acid substitutions outside of previously characterized FAD-binding motifs and the complementary StaC-10x. We find that these mutations mediate both FAD affinity and product specificity, with RebC-10x displaying higher StaC activity than StaC itself. X-ray structures of this StaC catalyst identify the substrate of StaC as 7-carboxy-K252c and suggest a unique mechanism for this FAD-dependent enzyme.
| + | |
| - | | + | |
| - | An Unusual Role for a Mobile Flavin in StaC-like Indolocarbazole Biosynthetic Enzymes.,Goldman PJ, Ryan KS, Hamill MJ, Howard-Jones AR, Walsh CT, Elliott SJ, Drennan CL Chem Biol. 2012 Jul 27;19(7):855-65. PMID:22840773<ref>PMID:22840773</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 4eiq" style="background-color:#fffaf0;"></div>
| + | |
| - | == References ==
| + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Drennan, C L]] | + | [[Category: Large Structures]] |
| - | [[Category: Elliott, S J]] | + | [[Category: Lentzea aerocolonigenes]] |
| - | [[Category: Goldman, P J]] | + | [[Category: Drennan CL]] |
| - | [[Category: Hamill, M J]] | + | [[Category: Elliott SJ]] |
| - | [[Category: Howard-Jones, A R]] | + | [[Category: Goldman PJ]] |
| - | [[Category: Ryan, K S]] | + | [[Category: Hamill MJ]] |
| - | [[Category: Walsh, C T]] | + | [[Category: Howard-Jones AR]] |
| - | [[Category: 7-carboxy-k252c]]
| + | [[Category: Ryan KS]] |
| - | [[Category: Flavin adenine dinucleotide]] | + | [[Category: Walsh CT]] |
| - | [[Category: Indolocarbazole]] | + | |
| - | [[Category: Monooxygenase]]
| + | |
| - | [[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
| + | |
