View source for 3pfg


==X-Ray crystal structure the N,N-dimethyltransferase TylM1 from Streptomyces fradiae in complex with SAM and dTDP-phenol==
<StructureSection load='3pfg' size='340' side='right'caption='[[3pfg]], [[Resolution|resolution]] 1.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3pfg]] 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=3PFG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PFG 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]] 1.349&#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=SAM:S-ADENOSYLMETHIONINE'>SAM</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=3pfg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pfg OCA], [https://pdbe.org/3pfg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3pfg RCSB], [https://www.ebi.ac.uk/pdbsum/3pfg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3pfg 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 ==
D-Mycaminose is an unusual dideoxysugar found attached to the antibiotic tylosin, a commonly used veterinarian therapeutic. It is synthesized by the Gram-positive bacterium, Streptomyces fradiae, as a dTDP-linked sugar. The last step in its biosynthesis involves the dimethylation of the hexose C-3' amino group by an S-adenosylmethionine (SAM) dependent enzyme referred to as TylM1. Here we report two high resolution X-ray structures of TylM1, one in which the enzyme contains bound SAM and dTDP-phenol, and the second in which the protein is complexed with S-adenosylhomocysteine (SAH) and dTDP-3-amino-3,6-dideoxyglucose, its natural substrate. Combined, these two structures, solved to 1.35-A and 1.79-A resolution, respectively, show the orientations of SAM and the dTDP-linked sugar substrate within the active site region. Specifically, the C-3' amino group of the hexose is in the correct position for an in-line attack at the reactive methyl group of SAM. Both Tyr 14 and Arg 241 serve to anchor the dTDP-linked sugar to the protein. To test the role of His 123 in catalysis, two site-directed mutant proteins were constructed, H123A and H123N. Both mutant proteins retained catalytic activity, albeit with reduced rates. Specifically, the kcat/Km was reduced to 1.8% and 0.37% for the H123A and H123N mutant proteins, respectively. High-resolution X-ray models showed that the observed perturbations in the kinetic constants were not due to major changes in their three-dimensional folds. Most likely the proton on the C-3' amino group is transferred to one of the water molecules lining the active site pocket as catalysis proceeds.

Molecular Architecture of TylM1 from Streptomyces fradiae: an N,N-Dimethyltransferase Involved in the Production of dTDP-D-Mycaminose.,Carney AE, Holden HM Biochemistry. 2010 Dec 13. PMID:21142177<ref>PMID:21142177</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3pfg" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces fradiae]]
[[Category: Carney AE]]
[[Category: Holden HM]]