View source for 6h43


==Flavin-dependent Tryptophan 6-halogenase Thal==
<StructureSection load='6h43' size='340' side='right' caption='[[6h43]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6h43]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_23875 Atcc 23875]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6H43 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6H43 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6ib5|6ib5]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">thal ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1887 ATCC 23875])</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=6h43 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6h43 OCA], [http://pdbe.org/6h43 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6h43 RCSB], [http://www.ebi.ac.uk/pdbsum/6h43 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6h43 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Flavin-dependent halogenases increasingly attract attention as biocatalysts in organic synthesis, facilitating environmentally friendly halogenation strategies that require only FADH2, oxygen and halide salts. Different flavin-dependent tryptophan halogenases regioselectively chlorinate or brominate tryptophan's indole moiety at C5, C6, or C7. Here, we present the first substrate-bound structure of a tryptophan 6-halogenase, namely Thal, also known as ThdH, from the bacterium Streptomyces albogriseolus at 2.55 A resolution. The structure revealed that the C6 of tryptophan is positioned next to the &epsilon;-amino group of a conserved lysine, confirming the hypothesis that proximity to the catalytic residue determines the site of electrophilic aromatic substitution. Although Thal is more similar in sequence and structure to the tryptophan 7-halogenase RebH than to the tryptophan 5-halogenase PyrH, the indole binding pose in the Thal active site more closely resembled that of PyrH than that of RebH. The difference in indole orientation between Thal and RebH appeared to be largely governed by residues positioning the Trp backbone atoms. The sequences of Thal and RebH lining the substrate binding site differ in only few residues. Therefore, we exchanged five amino acids in the Thal active site with the corresponding counterparts in RebH, generating the quintuple variant Thal-RebH5. Overall conversion of Trp by the Thal-RebH5 variant resembled that of wildtype Thal, but its regioselectivity of chlorination and bromination was almost completely switched from C6 to C7 as in RebH. We conclude that structure-based protein engineering with targeted substitution of a few residues is an efficient approach to tailoring flavin-dependent halogenases.

Structure-based switch of regioselectivity in the flavin-dependent tryptophan 6-halogenase Thal.,Moritzer AC, Minges H, Prior T, Frese M, Sewald N, Niemann HH J Biol Chem. 2018 Dec 17. pii: RA118.005393. doi: 10.1074/jbc.RA118.005393. PMID:30559288<ref>PMID:30559288</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6h43" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Atcc 23875]]
[[Category: Frese, M]]
[[Category: Minges, H]]
[[Category: Moritzer, A]]
[[Category: Niemann, H H]]
[[Category: Sewald, N]]
[[Category: Flavoprotein]]
[[Category: Thdh]]
[[Category: Tryptophan halogenase]]