1ev5: Difference between revisions

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-{{Seed}}
-[[Image:1ev5.png|left|200px]]
-<!--
+==CRYSTAL STRUCTURE ANALYSIS OF ALA167 MUTANT OF ESCHERICHIA COLI==
-The line below this paragraph, containing "STRUCTURE_1ev5", creates the "Structure Box" on the page.
+<StructureSection load='1ev5' size='340' side='right'caption='[[1ev5]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[1ev5]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EV5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EV5 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene>, <scene name='pdbligand=CXM:N-CARBOXYMETHIONINE'>CXM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-{{STRUCTURE_1ev5|  PDB=1ev5  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ev5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ev5 OCA], [https://pdbe.org/1ev5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ev5 RCSB], [https://www.ebi.ac.uk/pdbsum/1ev5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ev5 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/TYSY_ECOLI TYSY_ECOLI] Provides the sole de novo source of dTMP for DNA biosynthesis. This protein also binds to its mRNA thus repressing its own translation.
+== 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/ev/1ev5_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1ev5 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The role of Ser 167 of Escherichia coli thymidylate synthase (TS) in catalysis has been characterized by kinetic and crystallographic studies. Position 167 variants including S167A, S167N, S167D, S167C, S167G, S167L, S167T, and S167V were generated by site-directed mutagenesis. Only S167A, S167G, S167T, and S167C complemented the growth of thymidine auxotrophs of E. coli in medium lacking thymidine. Steady-state kinetic analysis revealed that mutant enzymes exhibited k(cat) values 1.1-95-fold lower than that of the wild-type enzyme. Relative to wild-type TS, K(m) values of the mutant enzymes for 2'-deoxyuridylate (dUMP) were 5-90 times higher, while K(m) values for 5,10-methylenetetrahydrofolate (CH(2)H(4)folate) were 1.5-16-fold higher. The rate of dehalogenation of 5-bromo-2'-deoxyuridine 5'-monophosphate (BrdUMP), a reaction catalyzed by TS that does not require CH(2)H(4)folate as cosubstrate, by mutant TSs was analyzed and showed that only S167A and S167G catalyzed the dehalogenation reaction and values of k(cat)/K(m) for the mutant enzymes were decreased by 10- and 3000-fold, respectively. Analysis of pre-steady-state kinetics of ternary complex formation revealed that the productive binding of CH(2)H(4)folate is weaker to mutant TSs than to the wild-type enzyme. Chemical transformation constants (k(chem)) for the mutant enzymes were lower by 1.1-6.0-fold relative to the wild-type enzyme. S167A, S167T, and S167C crystallized in the I2(1)3 space group and scattered X-rays to either 1.7 A (S167A and S167T) or 2.6 A (S167C). The high-resolution data sets were refined to a R(crys) of 19.9%. In the crystals some cysteine residues were derivatized with 2-mercaptoethanol to form S,S-(2-hydroxyethyl)thiocysteine. The pattern of derivatization indicates that in the absence of bound substrate the catalytic cysteine is not more reactive than other cysteines. It is proposed that the catalytic cysteine is activated by substrate binding by a proton-transfer mechanism in which the phosphate group of the nucleotide neutralizes the charge of Arg 126', facilitating the transfer of a proton from the catalytic cysteine to a His 207-Asp 205 diad via a system of ordered water molecules.
-===CRYSTAL STRUCTURE ANALYSIS OF ALA167 MUTANT OF ESCHERICHIA COLI===
+Catalytic cysteine of thymidylate synthase is activated upon substrate binding.,Phan J, Mahdavian E, Nivens MC, Minor W, Berger S, Spencer HT, Dunlap RB, Lebioda L Biochemistry. 2000 Jun 13;39(23):6969-78. PMID:10841779<ref>PMID:10841779</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 1ev5" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_10841779}}, adds the Publication Abstract to the page
+*[[Thymidylate synthase 3D structures|Thymidylate synthase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 10841779 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_10841779}}
+__TOC__
+</StructureSection>
-==About this Structure==
-EV5 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EV5 OCA].
-==Reference==
-Catalytic cysteine of thymidylate synthase is activated upon substrate binding., Phan J, Mahdavian E, Nivens MC, Minor W, Berger S, Spencer HT, Dunlap RB, Lebioda L, Biochemistry. 2000 Jun 13;39(23):6969-78. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10841779 10841779]
 [[Category: Escherichia coli]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Thymidylate synthase]]
+[[Category: Berger S]]
-[[Category: Berger, S.]]
+[[Category: Dunlap RB]]
-[[Category: Dunlap, R B.]]
+[[Category: Lebioda L]]
-[[Category: Lebioda, L.]]
+[[Category: Mahdavian E]]
-[[Category: Mahdavian, E.]]
+[[Category: Minor W]]
-[[Category: Minor, W.]]
+[[Category: Nivens MC]]
-[[Category: Nivens, M C.]]
+[[Category: Phan J]]
-[[Category: Phan, J.]]
+[[Category: Spencer HT]]
-[[Category: Spencer, H T.]]
-[[Category: Ala167 e. coli thymidylate synthase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul  1 02:04:13 2008''