5uao: Difference between revisions
New page: '''Unreleased structure''' The entry 5uao is ON HOLD Authors: Cogan, D.P., Nair, S.K. Description: Crystal structure of MibH, a lathipeptide tryptophan 5-halogenase [[Category: Unrelea... |
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The | ==Crystal structure of MibH, a lathipeptide tryptophan 5-halogenase== | ||
<StructureSection load='5uao' size='340' side='right'caption='[[5uao]], [[Resolution|resolution]] 1.88Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5uao]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Microbispora_sp._ATCC_PTA-5024 Microbispora sp. ATCC PTA-5024]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UAO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UAO 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]] 1.88Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</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=5uao FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uao OCA], [https://pdbe.org/5uao PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5uao RCSB], [https://www.ebi.ac.uk/pdbsum/5uao PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5uao ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/W2EQU4_9ACTN W2EQU4_9ACTN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Lantibiotics are ribosomally synthesized and post-translationally modified antimicrobial peptides containing thioether rings. In addition to these cross-links, the clinical candidate lantibiotic NAI-107 also possesses a C-terminal S-[(Z)-2-aminovinyl]-d-cysteine (AviCys) and a unique 5-chloro-l-tryptophan (ClTrp) moiety linked to its potent bioactivity. Bioinformatic and genetic analyses on the NAI-107 biosynthetic gene cluster identified mibH and mibD as genes encoding flavoenzymes responsible for the formation of ClTrp and AviCys, respectively. The biochemical basis for the installation of these modifications on NAI-107 and the substrate specificity of either enzyme is currently unknown. Using a combination of mass spectrometry, liquid chromatography, and bioinformatic analyses, we demonstrate that MibD is an FAD-dependent Cys decarboxylase and that MibH is an FADH2-dependent Trp halogenase. Most FADH2-dependent Trp halogenases halogenate free Trp, but MibH was only active when Trp was embedded within its cognate peptide substrate deschloro NAI-107. Structural comparison of the 1.88-A resolution crystal structure of MibH with other flavin-dependent Trp halogenases revealed that subtle amino acid differences within the MibH substrate binding site generates a solvent exposed crevice presumably involved in determining the substrate specificity of this unusual peptide halogenase. | |||
Two Flavoenzymes Catalyze the Post-Translational Generation of 5-Chlorotryptophan and 2-Aminovinyl-Cysteine during NAI-107 Biosynthesis.,Ortega MA, Cogan DP, Mukherjee S, Garg N, Li B, Thibodeaux GN, Maffioli SI, Donadio S, Sosio M, Escano J, Smith L, Nair SK, van der Donk WA ACS Chem Biol. 2017 Jan 13. doi: 10.1021/acschembio.6b01031. PMID:28032983<ref>PMID:28032983</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5uao" style="background-color:#fffaf0;"></div> | ||
[[Category: Cogan | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Microbispora sp. ATCC PTA-5024]] | |||
[[Category: Cogan DP]] | |||
[[Category: Nair SK]] | |||