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==A 1.68-A resolution 3-fluoro-L-tyrosine bound crystal structure of heme-dependent tyrosine hydroxylase==
<StructureSection load='7kqs' size='340' side='right'caption='[[7kqs]], [[Resolution|resolution]] 1.68&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KQS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KQS 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]] 1.677&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene>, <scene name='pdbligand=YOF:3-FLUOROTYROSINE'>YOF</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=7kqs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kqs OCA], [https://pdbe.org/7kqs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kqs RCSB], [https://www.ebi.ac.uk/pdbsum/7kqs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kqs ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
The heme-dependent l-tyrosine hydroxylases (TyrHs) in natural product biosynthesis constitute a new enzyme family in contrast to the nonheme iron enzymes for DOPA production. A representative TyrH exhibits dual reactivity of C-H and C-F bond cleavage when challenged with 3-fluoro-l-tyrosine (3-F-Tyr) as a substrate. However, little is known about how the enzyme mediates two distinct reactions. Herein, a new TyrH from the thermophilic bacterium Streptomyces sclerotialus (SsTyrH) was functionally and structurally characterized. A de novo crystal structure of the enzyme-substrate complex at 1.89-A resolution provides the first comprehensive structural study of this hydroxylase. The binding conformation of l-tyrosine indicates that C-H bond hydroxylation is initiated by electron transfer. Mutagenesis studies confirmed that an active site histidine, His88, participates in catalysis. We also obtained a 1.68-A resolution crystal structure in complex with the monofluorinated substrate, 3-F-Tyr, which shows one binding conformation but two orientations of the fluorine atom with a ratio of 7:3, revealing that the primary factor of product distribution is the substrate orientation. During in crystallo reaction, a ferric-hydroperoxo intermediate (compound 0, Fe(3+)-OOH) was observed with 3-F-Tyr as a substrate based on characteristic spectroscopic features. We determined the crystal structure of this compound 0-type intermediate and refined it to 1.58-A resolution. Collectively, this study provided the first molecular details of the heme-dependent TyrH and determined the primary factor that dictates the partitioning between the dual reactivities of C-H and C-F bond activation.

Molecular Rationale for Partitioning between C-H and C-F Bond Activation in Heme-Dependent Tyrosine Hydroxylase.,Wang Y, Davis I, Shin I, Xu H, Liu A J Am Chem Soc. 2021 Mar 18. doi: 10.1021/jacs.1c00175. PMID:33734681<ref>PMID:33734681</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Hydroxylases 3D structures|Hydroxylases 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Liu A]]
[[Category: Wang Y]]