View source for 6db2


==X-ray crystal structure of VioC bound to vanadyl ion, L-homoarginine, and succinate==
<StructureSection load='6db2' size='340' side='right'caption='[[6db2]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6db2]] 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=6DB2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DB2 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]] 1.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=HRG:L-HOMOARGININE'>HRG</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</scene>, <scene name='pdbligand=VVO:oxidanylidenevanadium(2+)'>VVO</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=6db2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6db2 OCA], [https://pdbe.org/6db2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6db2 RCSB], [https://www.ebi.ac.uk/pdbsum/6db2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6db2 ProSAT]</span></td></tr>
</table>
== Function ==
[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> 
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== 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 (&lt;/= 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6db2" style="background-color:#fffaf0;"></div>

==See Also==
*[[Hydroxylases 3D structures|Hydroxylases 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces vinaceus]]
[[Category: Boal AK]]
[[Category: Dunham NP]]
[[Category: Mitchell AJ]]