View source for 4hmz


==Crystal Structure of ChmJ, a 3'-monoepimerase from Streptomyces bikiniensis in complex with dTDP-quinovose==
<StructureSection load='4hmz' size='340' side='right'caption='[[4hmz]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4hmz]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_bikiniensis Streptomyces bikiniensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HMZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HMZ 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]] 2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=18T:[(2R,3S,5R)-3-HYDROXY-5-(5-METHYL-2,4-DIOXO-3,4-DIHYDROPYRIMIDIN-1(2H)-YL)TETRAHYDROFURAN-2-YL]METHYL+(2R,3R,4S,5S,6R)-3,4,5-TRIHYDROXY-6-METHYLTETRAHYDRO-2H-PYRAN-2-YL+DIHYDROGEN+DIPHOSPHATE'>18T</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=4hmz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hmz OCA], [https://pdbe.org/4hmz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hmz RCSB], [https://www.ebi.ac.uk/pdbsum/4hmz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hmz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CHMJ_STRBI CHMJ_STRBI] Catalyzes the conversion of dTDP-4-oxo-6-deoxyglucose to dTDP-4-oxo-6-deoxyallose, via a C-3 epimerization. This is a step in the biosynthesis of the mycinose moiety of the chalcomycin antibiotic.<ref>PMID:23116432</ref> 
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== Publication Abstract from PubMed ==
Unusual deoxy sugars are often attached to natural products such as antibiotics, antifungals, and chemotherapeutic agents. One such sugar is mycinose, which has been found on the antibiotics chalcomycin and tylosin. An intermediate in the biosynthesis of mycinose is dTDP-6-deoxy-d-allose. Four enzymes are required for the production of dTDP-6-deoxy-d-allose in Streptomyces bikiniensis, a soil-dwelling microbe first isolated from the Bikini and Rongelap atolls. Here we describe a combined structural and functional study of the enzyme ChmJ, which reportedly catalyzes the third step in the pathway leading to dTDP-6-deoxy-d-allose formation. Specifically, it has been proposed that ChmJ is a 3'-epimerase that converts dTDP-4-keto-6-deoxyglucose to dTDP-4-keto-6-deoxyallose. This activity, however, has never been verified in vitro. As reported here, we demonstrate using (1)H nuclear magnetic resonance that ChmJ, indeed, functions as a 3'-epimerase. In addition, we determined the structure of ChmJ complexed with dTDP-quinovose to 2.0 A resolution. The structure of ChmJ shows that it belongs to the well-characterized "cupin" superfamily. Two active site residues, His 60 and Tyr 130, were subsequently targeted for study via site-directed mutagenesis and kinetic analyses, and the three-dimensional architecture of the H60N/Y130F mutant protein was determined to 1.6 A resolution. Finally, the structure of the apoenzyme was determined to 2.2 A resolution. It has been previously suggested that the position of a conserved tyrosine, Tyr 130 in the case of ChmJ, determines whether an enzyme in this superfamily functions as a mono- or diepimerase. Our results indicate that the orientation of the tyrosine residue in ChmJ is a function of the ligand occupying the active site cleft.

Structural and Functional Studies on a 3'-Epimerase Involved in the Biosynthesis of dTDP-6-deoxy-d-allose.,Kubiak RL, Phillips RK, Zmudka MW, Ahn MR, Maka EM, Pyeatt GL, Roggensack SJ, Holden HM Biochemistry. 2012 Nov 20;51(46):9375-83. doi: 10.1021/bi3012737. Epub 2012 Nov, 9. PMID:23116432<ref>PMID:23116432</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4hmz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces bikiniensis]]
[[Category: Holden HM]]
[[Category: Kubiak RL]]