2vo1

From Proteopedia

(Difference between revisions)

Current revision

CRYSTAL STRUCTURE OF THE SYNTHETASE DOMAIN OF HUMAN CTP SYNTHETASE

Structural highlights

2vo1 is a 2 chain structure with sequence from Homo sapiens. This structure supersedes the now removed PDB entry 2c5m. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.8Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

PYRG1_HUMAN The disease is caused by mutations affecting the gene represented in this entry. A unique and recessive G to C mutation probably affecting a splice donor site at the junction of intron 17-18 and exon 18 has been identified in all patients. It results in expression of an abnormal transcript lacking exon 18 and a complete loss of the expression of the protein.^[1]

Function

PYRG1_HUMAN This enzyme is involved in the de novo synthesis of CTP, a precursor of DNA, RNA and phospholipids. Catalyzes the ATP-dependent amination of UTP to CTP with either L-glutamine or ammonia as a source of nitrogen. This enzyme and its product, CTP, play a crucial role in the proliferation of activated lymphocytes and therefore in immunity.^[2] ^[3]

Evolutionary Conservation

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

Publication Abstract from PubMed

Cytidine triphosphate synthetase (CTPS) is a key enzyme in nucleic acid and phospholipid biosynthesis and its activity is increased in certain human cancers, making it a promising drug target. The crystal structure of the synthetase domain of human CTPS, which represents the first structure of a CTPS from an eukaryote, has been determined. The structure is homotetrameric and each active site is formed by three different subunits. Sulfate ions bound to the active sites indicate the positions of phosphate-binding sites for the substrates ATP and UTP and the feedback inhibitor CTP. Together with earlier structures of bacterial CTPS, the human CTPS structure provides an extended understanding of the structure-function relationship of CTPS-family members. The structure also serves as a basis for structure-based design of anti-proliferative inhibitors.

Structure of the synthetase domain of human CTP synthetase, a target for anticancer therapy.,Kursula P, Flodin S, Ehn M, Hammarstrom M, Schuler H, Nordlund P, Stenmark P Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006 Jul 1;62(Pt, 7):613-7. Epub 2006 Jun 10. PMID:16820675^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Martin E, Palmic N, Sanquer S, Lenoir C, Hauck F, Mongellaz C, Fabrega S, Nitschke P, Esposti MD, Schwartzentruber J, Taylor N, Majewski J, Jabado N, Wynn RF, Picard C, Fischer A, Arkwright PD, Latour S. CTP synthase 1 deficiency in humans reveals its central role in lymphocyte proliferation. Nature. 2014 Jun 12;510(7504):288-92. doi: 10.1038/nature13386. Epub 2014 May 28. PMID:24870241 doi:http://dx.doi.org/10.1038/nature13386
↑ Han GS, Sreenivas A, Choi MG, Chang YF, Martin SS, Baldwin EP, Carman GM. Expression of Human CTP synthetase in Saccharomyces cerevisiae reveals phosphorylation by protein kinase A. J Biol Chem. 2005 Nov 18;280(46):38328-36. Epub 2005 Sep 22. PMID:16179339 doi:http://dx.doi.org/10.1074/jbc.M509622200
↑ Martin E, Palmic N, Sanquer S, Lenoir C, Hauck F, Mongellaz C, Fabrega S, Nitschke P, Esposti MD, Schwartzentruber J, Taylor N, Majewski J, Jabado N, Wynn RF, Picard C, Fischer A, Arkwright PD, Latour S. CTP synthase 1 deficiency in humans reveals its central role in lymphocyte proliferation. Nature. 2014 Jun 12;510(7504):288-92. doi: 10.1038/nature13386. Epub 2014 May 28. PMID:24870241 doi:http://dx.doi.org/10.1038/nature13386
↑ Kursula P, Flodin S, Ehn M, Hammarstrom M, Schuler H, Nordlund P, Stenmark P. Structure of the synthetase domain of human CTP synthetase, a target for anticancer therapy. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006 Jul 1;62(Pt, 7):613-7. Epub 2006 Jun 10. PMID:16820675 doi:http://dx.doi.org/10.1107/S1744309106018136

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2vo1"

@@ Line 3: / Line 3: @@
 <StructureSection load='2vo1' size='340' side='right'caption='[[2vo1]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2vo1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2c5m 2c5m]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VO1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VO1 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2vo1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2c5m 2c5m]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VO1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VO1 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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]] 2.8&#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;'>[[2c5m|2c5m]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/CTP_synthase_(glutamine_hydrolyzing) CTP synthase (glutamine hydrolyzing)], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.4.2 6.3.4.2] </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=2vo1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vo1 OCA], [https://pdbe.org/2vo1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vo1 RCSB], [https://www.ebi.ac.uk/pdbsum/2vo1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vo1 ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[https://www.uniprot.org/uniprot/PYRG1_HUMAN PYRG1_HUMAN] The disease is caused by mutations affecting the gene represented in this entry. A unique and recessive G to C mutation probably affecting a splice donor site at the junction of intron 17-18 and exon 18 has been identified in all patients. It results in expression of an abnormal transcript lacking exon 18 and a complete loss of the expression of the protein.<ref>PMID:24870241</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/PYRG1_HUMAN PYRG1_HUMAN] This enzyme is involved in the de novo synthesis of CTP, a precursor of DNA, RNA and phospholipids. Catalyzes the ATP-dependent amination of UTP to CTP with either L-glutamine or ammonia as a source of nitrogen. This enzyme and its product, CTP, play a crucial role in the proliferation of activated lymphocytes and therefore in immunity.<ref>PMID:16179339</ref> <ref>PMID:24870241</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 32: / Line 35: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Arrowsmith, C]]
+[[Category: Arrowsmith C]]
-[[Category: Berg, S Van Den]]
+[[Category: Berglund H]]
-[[Category: Berglund, H]]
+[[Category: Edwards A]]
-[[Category: Edwards, A]]
+[[Category: Ehn M]]
-[[Category: Ehn, M]]
+[[Category: Flodin S]]
-[[Category: Flodin, S]]
+[[Category: Graslund S]]
-[[Category: Graslund, S]]
+[[Category: Hallberg BM]]
-[[Category: Hallberg, B M]]
+[[Category: Hammarstrom M]]
-[[Category: Hammarstrom, M]]
+[[Category: Holmberg-Schiavone L]]
-[[Category: Holmberg-Schiavone, L]]
+[[Category: Kotenyoa T]]
-[[Category: Kotenyoa, T]]
+[[Category: Kursula P]]
-[[Category: Kursula, P]]
+[[Category: Moche M]]
-[[Category: Moche, M]]
+[[Category: Nilsson-Ehle P]]
-[[Category: Nilsson-Ehle, P]]
+[[Category: Nordlund P]]
-[[Category: Nordlund, P]]
+[[Category: Ogg D]]
-[[Category: Ogg, D]]
+[[Category: Persson C]]
-[[Category: Persson, C]]
+[[Category: Sagemark J]]
-[[Category: Sagemark, J]]
+[[Category: Schuler H]]
-[[Category: Schuler, H]]
+[[Category: Stenmark P]]
-[[Category: Stenmark, P]]
+[[Category: Sundstrom M]]
-[[Category: Sundstrom, M]]
+[[Category: Thorsell AG]]
-[[Category: Thorsell, A G]]
+[[Category: Van Den Berg S]]
-[[Category: Weigelt, J]]
+[[Category: Weigelt J]]
-[[Category: Amidotransferase]]
-[[Category: Ctp]]
-[[Category: Ctp synthase]]
-[[Category: Ctp synthetase]]
-[[Category: Cytidine 5-prime triphosphate synthetase]]
-[[Category: Glutamine]]
-[[Category: Glutamine amidotransferase]]
-[[Category: Ligase]]
-[[Category: Phosphoprotein]]
-[[Category: Phosphorylation]]
-[[Category: Pyrimidine biosynthesis]]
-[[Category: Utp]]

2vo1

From Proteopedia

Current revision

CRYSTAL STRUCTURE OF THE SYNTHETASE DOMAIN OF HUMAN CTP SYNTHETASE

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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