3px2: Difference between revisions
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==Structure of TylM1 from Streptomyces fradiae H123N mutant in complex with SAH and dTDP-Quip3N== | |||
<StructureSection load='3px2' size='340' side='right' caption='[[3px2]], [[Resolution|resolution]] 1.65Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3px2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Streptomyces_fradiae Streptomyces fradiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PX2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3PX2 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=T3Q:[(3R,4S,5S,6R)-4-AMINO-3,5-DIHYDROXY-6-METHYLOXAN-2-YL][HYDROXY-[[(2R,3S,5R)-3-HYDROXY-5-(5-METHYL-2,4-DIOXOPYRIMIDIN-1-YL)OXOLAN-2-YL]METHOXY]PHOSPHORYL]+HYDROGEN+PHOSPHATE'>T3Q</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3pfg|3pfg]], [[3pfh|3pfh]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">tylM1, tylMI(orf3*) ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1906 Streptomyces fradiae])</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=3px2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3px2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3px2 RCSB], [http://www.ebi.ac.uk/pdbsum/3px2 PDBsum]</span></td></tr> | |||
</table> | |||
<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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Streptomyces fradiae]] | [[Category: Streptomyces fradiae]] | ||
[[Category: Carney, A E | [[Category: Carney, A E]] | ||
[[Category: Holden, H M | [[Category: Holden, H M]] | ||
[[Category: Dtdp-quip3n binding]] | [[Category: Dtdp-quip3n binding]] | ||
[[Category: N-dimethyltransferase]] | [[Category: N-dimethyltransferase]] | ||
[[Category: Sam binding]] | [[Category: Sam binding]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
Revision as of 11:11, 19 December 2014
Structure of TylM1 from Streptomyces fradiae H123N mutant in complex with SAH and dTDP-Quip3N
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