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[[Image:1njb.gif|left|200px]]<br />
<applet load="1njb" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1njb, resolution 2.74&Aring;" />
'''THYMIDYLATE SYNTHASE'''<br />


==Overview==
==THYMIDYLATE SYNTHASE==
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.
<StructureSection load='1njb' size='340' side='right'caption='[[1njb]], [[Resolution|resolution]] 2.74&Aring;' scene=''>
== Structural highlights ==
<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>
</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>
<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>
<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>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TYSY_LACCA TYSY_LACCA] Provides the sole de novo source of dTMP for DNA biosynthesis.
== 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/nj/1njb_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=1njb ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1NJB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Lactobacillus_casei Lactobacillus casei] with UMP as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Structure known Active Site: CAT. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1NJB OCA].
*[[Thymidylate synthase 3D structures|Thymidylate synthase 3D structures]]
 
__TOC__
==Reference==
</StructureSection>
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://ispc.weizmann.ac.il//pmbin/getpm?pmid=8611496 8611496]
[[Category: Lacticaseibacillus casei]]
[[Category: Lactobacillus casei]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Finer-Moore J]]
[[Category: Thymidylate synthase]]
[[Category: Stroud RM]]
[[Category: Finer-Moore, J.]]
[[Category: Stroud, R.M.]]
[[Category: UMP]]
[[Category: methyltransferase]]
[[Category: nucleotide biosynthesis]]
[[Category: transferase]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov  5 16:44:03 2007''

Latest revision as of 10:57, 14 February 2024

THYMIDYLATE SYNTHASETHYMIDYLATE SYNTHASE

Structural highlights

1njb is a 1 chain structure with sequence from Lacticaseibacillus casei. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.74Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TYSY_LACCA Provides the sole de novo source of dTMP for DNA biosynthesis.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

1njb, resolution 2.74Å

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