5u03

From Proteopedia

(Difference between revisions)

Current revision

Cryo-EM structure of the human CTP synthase filament

5u03, resolution 6.10Å

Structural highlights

5u03 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:	Electron Microscopy, Resolution 6.1Å
Ligands:
Experimental data:	Check to display Experimental Data
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]

Publication Abstract from PubMed

The universally conserved enzyme CTP synthase (CTPS) forms filaments in bacteria and eukaryotes. In bacteria, polymerization inhibits CTPS activity and is required for nucleotide homeostasis. Here we show that for human CTPS, polymerization increases catalytic activity. The cryo-EM structures of bacterial and human CTPS filaments differ considerably in overall architecture and in the conformation of the CTPS protomer, explaining the divergent consequences of polymerization on activity. The structure of human CTPS filament, the first structure of the full-length human enzyme, reveals a novel active conformation. The filament structures elucidate allosteric mechanisms of assembly and regulation that rely on a conserved conformational equilibrium. The findings may provide a mechanism for increasing human CTPS activity in response to metabolic state and challenge the assumption that metabolic filaments are generally storage forms of inactive enzymes. Allosteric regulation of CTPS polymerization by ligands likely represents a fundamental mechanism underlying assembly of other metabolic filaments.

Human CTP synthase filament structure reveals the active enzyme conformation.,Lynch EM, Hicks DR, Shepherd M, Endrizzi JA, Maker A, Hansen JM, Barry RM, Gitai Z, Baldwin EP, Kollman JM Nat Struct Mol Biol. 2017 May 1. doi: 10.1038/nsmb.3407. PMID:28459447^[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
↑ Lynch EM, Hicks DR, Shepherd M, Endrizzi JA, Maker A, Hansen JM, Barry RM, Gitai Z, Baldwin EP, Kollman JM. Human CTP synthase filament structure reveals the active enzyme conformation. Nat Struct Mol Biol. 2017 May 1. doi: 10.1038/nsmb.3407. PMID:28459447 doi:http://dx.doi.org/10.1038/nsmb.3407

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5u03"

Categories: Homo sapiens | Large Structures | Kollman JM | Lynch EM

@@ Line 3: / Line 3: @@
 <SX load='5u03' size='340' side='right' viewer='molstar' caption='[[5u03]], [[Resolution|resolution]] 6.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5u03]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U03 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5U03 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5u03]] 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=5U03 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5U03 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=UTP:URIDINE+5-TRIPHOSPHATE'>UTP</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 6.1&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5u05|5u05]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=UTP:URIDINE+5-TRIPHOSPHATE'>UTP</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CTPS1, CTPS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5u03 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u03 OCA], [https://pdbe.org/5u03 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5u03 RCSB], [https://www.ebi.ac.uk/pdbsum/5u03 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5u03 ProSAT]</span></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/CTP_synthase_(glutamine_hydrolyzing) CTP synthase (glutamine hydrolyzing)], with EC number [http://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'>[http://proteopedia.org/fgij/fg.htm?mol=5u03 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u03 OCA], [http://pdbe.org/5u03 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u03 RCSB], [http://www.ebi.ac.uk/pdbsum/5u03 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u03 ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://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>
+[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 ==
-[[http://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>
+[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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 27: / Line 25: @@
 __TOC__
 </SX>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Kollman, J M]]
+[[Category: Kollman JM]]
-[[Category: Lynch, E M]]
+[[Category: Lynch EM]]
-[[Category: Enzyme]]
-[[Category: Filament]]
-[[Category: Ligase]]
-[[Category: Nucleotide metabolism]]
-[[Category: Protein fibril]]

5u03

From Proteopedia

Current revision

Cryo-EM structure of the human CTP synthase filament

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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