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==THYMIDYLATE SYNTHASE, MUTATION, N229D WITH 2'-DEOXYCYTIDINE 5'-MONOPHOSPHATE (DCMP)==
==THYMIDYLATE SYNTHASE, MUTATION, N229D WITH 2'-DEOXYCYTIDINE 5'-MONOPHOSPHATE (DCMP)==
<StructureSection load='1njc' size='340' side='right' caption='[[1njc]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
<StructureSection load='1njc' size='340' side='right'caption='[[1njc]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1njc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_a"_von_freudenreich_1890 "bacillus a" von freudenreich 1890]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NJC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1NJC FirstGlance]. <br>
<table><tr><td colspan='2'>[[1njc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lacticaseibacillus_casei Lacticaseibacillus casei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NJC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NJC FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DCM:2-DEOXYCYTIDINE-5-MONOPHOSPHATE'>DCM</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">N229D MUTANT OF CLONED L. CASE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1582 "Bacillus a" von Freudenreich 1890])</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DCM:2-DEOXYCYTIDINE-5-MONOPHOSPHATE'>DCM</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thymidylate_synthase Thymidylate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.45 2.1.1.45] </span></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=1njc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1njc OCA], [https://pdbe.org/1njc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1njc RCSB], [https://www.ebi.ac.uk/pdbsum/1njc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1njc ProSAT]</span></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=1njc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1njc OCA], [http://pdbe.org/1njc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1njc RCSB], [http://www.ebi.ac.uk/pdbsum/1njc PDBsum]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/TYSY_LACCA TYSY_LACCA]] Provides the sole de novo source of dTMP for DNA biosynthesis.  
[https://www.uniprot.org/uniprot/TYSY_LACCA TYSY_LACCA] Provides the sole de novo source of dTMP for DNA biosynthesis.
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nj/1njc_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nj/1njc_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </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/chain_selection.php?pdb_ID=2ata ConSurf].
</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=1njc ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Thymidylate synthase (TS) methylates only dUMP, not dCMP. The crystal structure of TS.dCMP shows sCMP 4-NH2 excluded from the space between Asn-229 and His-199 by the hydrogen bonding and steric properties and Asn-229. Consequently, 6-C of dCMP is over 4 A from the active site sulfhydryl. The Asn-229 side chain is prevented from flipping 180 degrees to and orientation the could hydrogen bond to dCMP by a hydrogen bond network between conserved residues. Thus, the specific binding of dUMP by TS results from occlusion of competing substrates by steric and electronic effects of residues in the active site cavity. When Asn-229 is replaced by a cysteine, the Cys-229 S gamma rotates out of the active site, and the mutant enzyme binds both dCMP and dUMP tightly but does not methylate dCMP. Thus simply admitting dCMP into the dUMP binding site of TS is not sufficient for methylation of dCMP. Structures of nucleotide complexes of TS N229D provide a reasonable explanation for the preferential methylation of dCMP instead of dUMP by this mutant. In TS N229D.dCMP, Asp-229 forms hydrogen bonds to 3-N and 40NH2 of dCMP. Neither the Asp-229 carboxyl moiety nor ordered water appears to hydrogen bond to 4-O of dUMP. Hydrogen bonds to 4-O (or 4-NH2) have been proposed to stabilize reaction intermediates. If their absence in TS N229D.dUMP persists in the ternary complex, it could explain the 10(4)-fold decrease in kcat/Km for dUMP.
Partitioning roles of side chains in affinity, orientation, and catalysis with structures for mutant complexes: asparagine-229 in thymidylate synthase.,Finer-Moore JS, Liu L, Schafmeister CE, Birdsall DL, Mau T, Santi DV, Stroud RM Biochemistry. 1996 Apr 23;35(16):5125-36. PMID:8611496<ref>PMID:8611496</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1njc" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Thymidylate synthase|Thymidylate synthase]]
*[[Thymidylate synthase 3D structures|Thymidylate synthase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Bacillus a von freudenreich 1890]]
[[Category: Lacticaseibacillus casei]]
[[Category: Thymidylate synthase]]
[[Category: Large Structures]]
[[Category: Finer-Moore, J]]
[[Category: Finer-Moore J]]
[[Category: Stroud, R M]]
[[Category: Stroud RM]]
[[Category: Methyltransferase]]
[[Category: Nucleotide biosynthesis]]
[[Category: Transferase]]

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