|
|
| Line 3: |
Line 3: |
| <StructureSection load='6dax' size='340' side='right'caption='[[6dax]], [[Resolution|resolution]] 1.70Å' scene=''> | | <StructureSection load='6dax' size='340' side='right'caption='[[6dax]], [[Resolution|resolution]] 1.70Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6dax]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Streptomyces_vinaceus Streptomyces vinaceus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DAX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DAX FirstGlance]. <br> | | <table><tr><td colspan='2'>[[6dax]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_vinaceus Streptomyces vinaceus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DAX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DAX FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AKG:2-OXOGLUTARIC+ACID'>AKG</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=HRG:L-HOMOARGININE'>HRG</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]] 1.7Å</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=1.14.11.41 1.14.11.41] </span></td></tr>
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AKG:2-OXOGLUTARIC+ACID'>AKG</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=HRG:L-HOMOARGININE'>HRG</scene></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=6dax FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dax OCA], [http://pdbe.org/6dax PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dax RCSB], [http://www.ebi.ac.uk/pdbsum/6dax PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dax ProSAT]</span></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=6dax FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dax OCA], [https://pdbe.org/6dax PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dax RCSB], [https://www.ebi.ac.uk/pdbsum/6dax PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dax ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/ARGHX_STRVI ARGHX_STRVI]] Involved in the biosynthesis of capreomycidine, an unusual amino acid used by non-ribosomal peptide synthases (NRPS) to make the tuberactinomycin class of peptide antibiotics such as viomycin and capreomycin. Catalyzes the stereospecific hydroxylation of the C3 of (2S)-arginine to generate (3S)-hydroxy-(2S)-arginine. Usually clavaminic acid synthase-like oxygenases catalyze the formation of threo diastereomers, however VioC produces the erythro diastereomer of beta-carbon-hydroxylated L-arginine. It exerts a broad substrate specificity by accepting the analogs L-homoarginine and L-canavanine for the beta-carbon hydroxylation.<ref>PMID:15368580</ref> <ref>PMID:15368582</ref> <ref>PMID:19490124</ref> | | [https://www.uniprot.org/uniprot/ARGHX_STRVI ARGHX_STRVI] Involved in the biosynthesis of capreomycidine, an unusual amino acid used by non-ribosomal peptide synthases (NRPS) to make the tuberactinomycin class of peptide antibiotics such as viomycin and capreomycin. Catalyzes the stereospecific hydroxylation of the C3 of (2S)-arginine to generate (3S)-hydroxy-(2S)-arginine. Usually clavaminic acid synthase-like oxygenases catalyze the formation of threo diastereomers, however VioC produces the erythro diastereomer of beta-carbon-hydroxylated L-arginine. It exerts a broad substrate specificity by accepting the analogs L-homoarginine and L-canavanine for the beta-carbon hydroxylation.<ref>PMID:15368580</ref> <ref>PMID:15368582</ref> <ref>PMID:19490124</ref> |
| <div style="background-color:#fffaf0;">
| |
| == Publication Abstract from PubMed ==
| |
| Hydroxylation of aliphatic carbons by non-heme Fe(IV)-oxo (ferryl) complexes proceeds by hydrogen-atom (H*) transfer (HAT) to the ferryl and subsequent coupling between the carbon radical and Fe(III)-coordinated oxygen (termed rebound). Enzymes that use H*-abstracting ferryl complexes for other transformations must either suppress rebound or further process hydroxylated intermediates. For olefin-installing C-C desaturations, it has been proposed that a second HAT to the Fe(III)-OH complex from the carbon alpha to the radical preempts rebound. Deuterium ((2)H) at the second site should slow this step, potentially making rebound competitive. Desaturations mediated by two related L-arginine-modifying iron(II)- and 2-(oxo)glutarate-dependent (Fe/2OG) oxygenases behave oppositely in this key test, implicating different mechanisms. NapI, the L-Arg 4,5-desaturase from the naphthyridinomycin biosynthetic pathway, abstracts H* first from C5 but hydroxylates this site (leading to guanidine release) to the same modest extent whether C4 harbors (1)H or (2)H. By contrast, an unexpected 3,4-desaturation of L-homoarginine (L-hArg) by VioC, the L-Arg 3-hydroxylase from the viomycin biosynthetic pathway, is markedly disfavored relative to C4 hydroxylation when C3 (the second hydrogen donor) harbors (2)H. Anchimeric assistance by N6 permits removal of the C4-H as a proton in the NapI reaction, but, with no such assistance possible in the VioC desaturation, a second HAT step (from C3) is required. The close proximity (</= 3.5 A) of both L-hArg carbons to the (hydr)oxo group in an x-ray crystal structure of VioC harboring a vanadium-based ferryl mimic supports and rationalizes the sequential-HAT mechanism. The results suggest that, although the sequential-HAT mechanism is feasible, its geometric requirements may ensure competing hydroxylation, thus explaining why nearly all natural substrates for Fe/2OG desaturases have alpha-heteroatoms.
| |
| | |
| Two Distinct Mechanisms for C-C Desaturation by Iron(II)- and 2-(Oxo)glutarate-Dependent Oxygenases: Importance of alpha-Heteroatom Assistance.,Dunham NP, Chang WC, Mitchell AJ, Martinie RJ, Zhang B, Bergman JA, Rajakovich LJ, Wang B, Silakov A, Krebs C, Boal AK, Bollinger JM Jr J Am Chem Soc. 2018 Apr 30. doi: 10.1021/jacs.8b01933. PMID:29708749<ref>PMID:29708749</ref>
| |
| | |
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| |
| </div>
| |
| <div class="pdbe-citations 6dax" style="background-color:#fffaf0;"></div>
| |
|
| |
|
| ==See Also== | | ==See Also== |
| Line 27: |
Line 18: |
| </StructureSection> | | </StructureSection> |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Oxidoreductase]]
| |
| [[Category: Streptomyces vinaceus]] | | [[Category: Streptomyces vinaceus]] |
| [[Category: Boal, A K]] | | [[Category: Boal AK]] |
| [[Category: Dunham, N P]] | | [[Category: Dunham NP]] |
| [[Category: Mitchell, A J]] | | [[Category: Mitchell AJ]] |
| [[Category: Desaturase]]
| |
| [[Category: Desaturation]]
| |
| [[Category: Hydroxylase]]
| |
| [[Category: Hydroxylation]]
| |
| [[Category: Metalloenzyme]]
| |
| [[Category: Oxygenase]]
| |
| [[Category: Viomycin]]
| |