3gg5: Difference between revisions

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<StructureSection load='3gg5' size='340' side='right'caption='[[3gg5]], [[Resolution|resolution]] 2.77&Aring;' scene=''>
<StructureSection load='3gg5' size='340' side='right'caption='[[3gg5]], [[Resolution|resolution]] 2.77&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3gg5]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GG5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GG5 FirstGlance]. <br>
<table><tr><td colspan='2'>[[3gg5]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GG5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GG5 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.77&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1hw3|1hw3]], [[3eaw|3eaw]], [[3ebu|3ebu]], [[3ed7|3ed7]], [[3edw|3edw]], [[3ef9|3ef9]], [[3ejl|3ejl]], [[3gh0|3gh0]], [[3gh2|3gh2]]</div></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">OK/SW-cl.29, TS, TYMS ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Thymidylate_synthase Thymidylate synthase], with EC number [https://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=3gg5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gg5 OCA], [https://pdbe.org/3gg5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gg5 RCSB], [https://www.ebi.ac.uk/pdbsum/3gg5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gg5 ProSAT]</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=3gg5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gg5 OCA], [https://pdbe.org/3gg5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gg5 RCSB], [https://www.ebi.ac.uk/pdbsum/3gg5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gg5 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/TYSY_HUMAN TYSY_HUMAN]] Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.<ref>PMID:21876188</ref>
[https://www.uniprot.org/uniprot/TYSY_HUMAN TYSY_HUMAN] Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.<ref>PMID:21876188</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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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=3gg5 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=3gg5 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human and other mammalian thymidylate synthase (TS) enzymes have an N-terminal extension of approximately 27 amino acids that is not present in bacterial TSs. The extension, which is disordered in all reported crystal structures of TSs, has been considered to play a primary role in protein turnover but not in catalytic activity. In mammalian cells, the variant V3A has a half-life similar to that of wild-type human TS (wt hTS) while V3T is much more stable; V3L, V3F, and V3Y have half-lives approximately half of that for wt hTS. Catalytic turnover rates for most Val3 mutants are only slightly diminished, as expected. However, two mutants, V3L and V3F, have strongly compromised dUMP binding, with K(m,app) values increased by factors of 47 and 58, respectively. For V3L, this observation can be explained by stabilization of the inactive conformation of the loop of residues 181-197, which prevents substrate binding. In the crystal structure of V3L, electron density corresponding to a leucine residue is present in a position that stabilizes the loop of residues 181-197 in the inactive conformation. Since this density is not observed in other mutants and all other leucine residues are ordered in this structure, it is likely that this density represents Leu3. In the crystal structure of a V3F.FdUMP binary complex, the nucleotide is bound in an alternative mode to that proposed for the catalytic complex, indicating that the high K(m,app) value is caused not by stabilization of the inactive conformer but by substrate binding in a nonproductive, inhibitory site. These observations show that the N-terminal extension affects the conformational state of the hTS catalytic region. Each of the mechanisms leading to the high K(m,app) values can be exploited to facilitate design of compounds acting as allosteric inhibitors of hTS.
Replacement of Val3 in Human Thymidylate Synthase Affects Its Kinetic Properties and Intracellular Stability .,Huang X, Gibson LM, Bell BJ, Lovelace LL, Pena MM, Berger FG, Berger SH, Lebioda L Biochemistry. 2010 Feb 25. PMID:20151707<ref>PMID:20151707</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3gg5" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Thymidylate synthase]]
[[Category: Bell BJ]]
[[Category: Bell, B J]]
[[Category: Gibson LM]]
[[Category: Gibson, L M]]
[[Category: Huang X]]
[[Category: Huang, X]]
[[Category: Lebioda L]]
[[Category: Lebioda, L]]
[[Category: Lovelace LL]]
[[Category: Lovelace, L L]]
[[Category: Methyltransferase]]
[[Category: Nucleotide biosynthesis]]
[[Category: Transferase]]

Latest revision as of 12:54, 21 February 2024

Replacement of Val3 in Human Thymidylate Synthase Affects Its Kinetic Properties and Intracellular StabilityReplacement of Val3 in Human Thymidylate Synthase Affects Its Kinetic Properties and Intracellular Stability

Structural highlights

3gg5 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.77Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TYSY_HUMAN Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.[1]

Evolutionary Conservation

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

See Also

References

  1. ↑ Anderson DD, Quintero CM, Stover PJ. Identification of a de novo thymidylate biosynthesis pathway in mammalian mitochondria. Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15163-8. doi:, 10.1073/pnas.1103623108. Epub 2011 Aug 26. PMID:21876188 doi:10.1073/pnas.1103623108

3gg5, resolution 2.77Å

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