1mp5: Difference between revisions

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-[[Image:1mp5.jpg|left|200px]]<br /><applet load="1mp5" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1mp5, resolution 2.75&Aring;" />
-'''Y177F VARIANT OF S. ENTERICA RmlA'''<br />
-==Overview==
+==Y177F VARIANT OF S. ENTERICA RmlA==
-In vitro "glycorandomization" is a chemoenzymatic approach for generating, diverse libraries of glycosylated biomolecules based on natural product, scaffolds. This technology makes use of engineered variants of specific, enzymes affecting metabolite glycosylation, particularly, nucleotidylyltransferases and glycosyltransferases. To expand the, repertoire of UDP/dTDP sugars readily available for glycorandomization, we, now report a structure-based engineering approach to increase the, diversity of alpha-d-hexopyranosyl phosphates accepted by Salmonella, enterica LT2 alpha-d-glucopyranosyl phosphate thymidylyltransferase, (E(p)). This article highlights the design rationale, determined substrate, specificity, and structural elucidation of three "designed" mutations, illustrating both the success and unexpected outcomes from this type of, approach. In addition, a single amino acid substitution in the, substrate-binding pocket (L89T) was found to significantly increase the, set of alpha-d-hexopyranosyl phosphates accepted by E(p) to include, alpha-d-allo-, alpha-d-altro-, and alpha-d-talopyranosyl phosphate. In, aggregate, our results provide valuable blueprints for altering, nucleotidylyltransferase specificity by design, which is the first step, toward in vitro glycorandomization.
+<StructureSection load='1mp5' size='340' side='right'caption='[[1mp5]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1mp5]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Salmonella_enterica Salmonella enterica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MP5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MP5 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]] 2.75&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UPG:URIDINE-5-DIPHOSPHATE-GLUCOSE'>UPG</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=1mp5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mp5 OCA], [https://pdbe.org/1mp5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mp5 RCSB], [https://www.ebi.ac.uk/pdbsum/1mp5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mp5 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/RMLA_SALTY RMLA_SALTY] Catalyzes the formation of dTDP-glucose, from dTTP and glucose 1-phosphate, as well as its pyrophosphorolysis. Is also able to convert non natural substrates such as a wide array of alpha-D-hexopyranosyl, deoxy-alpha-D-glucopyranosyl, aminodeoxy-alpha-D-hexopyranosyl and acetamidodeoxy-alpha-D-hexopyranosyl phosphates to their corresponding dTDP- and UDP-nucleotide sugars.<ref>PMID:8382158</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mp/1mp5_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1mp5 ConSurf].
+<div style="clear:both"></div>
-==About this Structure==
+==See Also==
-MP5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Salmonella_enterica Salmonella enterica] with UPG as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Glucose-1-phosphate_thymidylyltransferase Glucose-1-phosphate thymidylyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.24 2.7.7.24] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1MP5 OCA].
+*[[Glucose-1-phosphate thymidylyltransferase 3D structures|Glucose-1-phosphate thymidylyltransferase 3D structures]]
+== References ==
-==Reference==
+<references/>
-Expanding pyrimidine diphosphosugar libraries via structure-based nucleotidylyltransferase engineering., Barton WA, Biggins JB, Jiang J, Thorson JS, Nikolov DB, Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13397-402. Epub 2002 Oct 8. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12374866 12374866]
+__TOC__
-[[Category: Glucose-1-phosphate thymidylyltransferase]]
+</StructureSection>
+[[Category: Large Structures]]
 [[Category: Salmonella enterica]]
-[[Category: Single protein]]
+[[Category: Barton WA]]
-[[Category: Barton, W.A.]]
+[[Category: Biggins JB]]
-[[Category: Biggins, J.B.]]
+[[Category: Jiang J]]
-[[Category: Jiang, J.]]
+[[Category: Nikolov DB]]
-[[Category: Nikolov, D.B.]]
+[[Category: Thorson JS]]
-[[Category: Thorson, J.S.]]
-[[Category: UPG]]
-[[Category: transferase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sat Nov 24 21:46:57 2007''