View source for 6m82


==Crystal structure of TylM1 Y14paF bound to SAH and dTDP-phenol==
<StructureSection load='6m82' size='340' side='right'caption='[[6m82]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6m82]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_fradiae Streptomyces fradiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6M82 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6M82 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]] 1.3971&#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=HOX:4-AMINO-L-PHENYLALANINE'>HOX</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=TLO:5-O-[(S)-HYDROXY{[(S)-HYDROXY(PHENOXY)PHOSPHORYL]OXY}PHOSPHORYL]THYMIDINE'>TLO</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=6m82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m82 OCA], [https://pdbe.org/6m82 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6m82 RCSB], [https://www.ebi.ac.uk/pdbsum/6m82 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6m82 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TYLM1_STRFR TYLM1_STRFR] S-adenosyl-L-methionine-dependent methyltransferase involved in the biosynthesis of mycaminose, an essential structural component of the macrolide antibiotic tylosin. Involved in the last step in mycaminose biosynthesis by mediating dimethylation of the hexose C-3' amino group.<ref>PMID:9031628</ref> <ref>PMID:12119032</ref> <ref>PMID:21142177</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The N-methyltransferase TylM1 from Streptomyces fradiae catalyzes the final step in the biosynthesis of the deoxyamino sugar mycaminose, a substituent of the antibiotic tylosin. The high-resolution crystal structure of TylM1 bound to the methyl donor S-adenosylmethionine (AdoMet) illustrates a network of carbon-oxygen (CH***O) hydrogen bonds between the substrate's sulfonium cation and residues within the active site. These interactions include hydrogen bonds between the methyl and methylene groups of the AdoMet sulfonium cation and the hydroxyl groups of Tyr14 and Ser120 in the enzyme. To examine the functions of these interactions, we generated Tyr14 to phenylalanine (Y14F) and Ser120 to alanine (S120A) mutations to selectively ablate the CH***O hydrogen bonding to AdoMet. The TylM1 S120A mutant exhibited a modest decrease in the catalytic efficiency relative to wild type (WT) enzyme, whereas the Y14F mutation resulted in an approximately 30-fold decrease in catalytic efficiency. In contrast, site-specific substitution of Tyr14 by the noncanonical amino acid p-aminophenylalanine partially restored activity comparable to the WT enzyme. Correlatively, quantum mechanical calculations of the activation barrier energies of WT TylM1 and the Tyr14 mutants suggest that substitutions which abrogate hydrogen bonding with the AdoMet methyl group impair methyl transfer. Together, these results offer insights into roles of CH***O hydrogen bonding in modulating the catalytic efficiency of TylM1.

Structural and Functional Characterization of Sulfonium Carbon-Oxygen Hydrogen Bonding in the Deoxyamino Sugar Methyltransferase TylM1.,Fick RJ, Horowitz S, McDole BG, Clay MC, Mehl RA, Al-Hashimi HM, Scheiner S, Trievel RC Biochemistry. 2019 Feb 27. doi: 10.1021/acs.biochem.8b01141. PMID:30810306<ref>PMID:30810306</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6m82" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces fradiae]]
[[Category: Fick RJ]]
[[Category: McDole BG]]
[[Category: Trievel RC]]