1njc: Difference between revisions

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[[Image:1njc.gif|left|200px]]


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==THYMIDYLATE SYNTHASE, MUTATION, N229D WITH 2'-DEOXYCYTIDINE 5'-MONOPHOSPHATE (DCMP)==
The line below this paragraph, containing "STRUCTURE_1njc", creates the "Structure Box" on the page.
<StructureSection load='1njc' size='340' side='right'caption='[[1njc]], [[Resolution|resolution]] 2.50&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'>[[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>
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]] 2.5&#8491;</td></tr>
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<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>
{{STRUCTURE_1njc| PDB=1njc |  SCENE= }}
<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>
</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/1njc_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=1njc ConSurf].
<div style="clear:both"></div>


'''THYMIDYLATE SYNTHASE, MUTATION, N229D WITH 2'-DEOXYCYTIDINE 5'-MONOPHOSPHATE (DCMP)'''
==See Also==
 
*[[Thymidylate synthase 3D structures|Thymidylate synthase 3D structures]]
 
__TOC__
==Overview==
</StructureSection>
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.
[[Category: Lacticaseibacillus casei]]
 
[[Category: Large Structures]]
==About this Structure==
[[Category: Finer-Moore J]]
1NJC 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=1NJC OCA].
[[Category: Stroud RM]]
 
==Reference==
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]
[[Category: Lactobacillus casei]]
[[Category: Single protein]]
[[Category: Thymidylate synthase]]
[[Category: Finer-Moore, J.]]
[[Category: Stroud, R M.]]
[[Category: Methyltransferase]]
[[Category: Nucleotide biosynthesis]]
[[Category: Transferase]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 02:36:05 2008''

Latest revision as of 10:57, 14 February 2024

THYMIDYLATE SYNTHASE, MUTATION, N229D WITH 2'-DEOXYCYTIDINE 5'-MONOPHOSPHATE (DCMP)THYMIDYLATE SYNTHASE, MUTATION, N229D WITH 2'-DEOXYCYTIDINE 5'-MONOPHOSPHATE (DCMP)

Structural highlights

1njc 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 2.5Å
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

1njc, resolution 2.50Å

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