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1njb

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[[Image:1njb.gif|left|200px]]
 
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{{Structure
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==THYMIDYLATE SYNTHASE==
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|PDB= 1njb |SIZE=350|CAPTION= <scene name='initialview01'>1njb</scene>, resolution 2.74&Aring;
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<StructureSection load='1njb' size='340' side='right'caption='[[1njb]], [[Resolution|resolution]] 2.74&Aring;' scene=''>
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|SITE= <scene name='pdbsite=CAT:Catalytic+CYS'>CAT</scene>
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=UMP:2&#39;-DEOXYURIDINE 5&#39;-MONOPHOSPHATE'>UMP</scene>
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<table><tr><td colspan='2'>[[1njb]] 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=1NJB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NJB FirstGlance]. <br>
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|ACTIVITY= [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]
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.74&#8491;</td></tr>
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|GENE= N229C MUTANT OF CLONED L. CASE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1582 Lactobacillus casei])
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</scene></td></tr>
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}}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1njb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1njb OCA], [https://pdbe.org/1njb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1njb RCSB], [https://www.ebi.ac.uk/pdbsum/1njb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1njb ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/TYSY_LACCA TYSY_LACCA] Provides the sole de novo source of dTMP for DNA biosynthesis.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nj/1njb_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1njb ConSurf].
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<div style="clear:both"></div>
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'''THYMIDYLATE SYNTHASE'''
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==See Also==
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*[[Thymidylate synthase 3D structures|Thymidylate synthase 3D structures]]
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__TOC__
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==Overview==
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</StructureSection>
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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.
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[[Category: Lacticaseibacillus casei]]
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[[Category: Large Structures]]
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==About this Structure==
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[[Category: Finer-Moore J]]
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1NJB is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Lactobacillus_casei Lactobacillus casei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NJB OCA].
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[[Category: Stroud RM]]
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==Reference==
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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:[http://www.ncbi.nlm.nih.gov/pubmed/8611496 8611496]
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[[Category: Lactobacillus casei]]
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[[Category: Single protein]]
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[[Category: Thymidylate synthase]]
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[[Category: Finer-Moore, J.]]
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[[Category: Stroud, R M.]]
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[[Category: UMP]]
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[[Category: methyltransferase]]
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[[Category: nucleotide biosynthesis]]
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[[Category: transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 23 12:54:44 2008''
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THYMIDYLATE SYNTHASE

PDB ID 1njb

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