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6pk4

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Revision as of 04:29, 11 April 2020

cryoEM structure of the substrate-bound human CTP synthase 2 filament

6pk4, resolution 3.50Å

Structural highlights

6pk4 is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	CTPS2 (HUMAN)
Activity:	CTP synthase (glutamine hydrolyzing), with EC number 6.3.4.2
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PYRG2_HUMAN] Catalyzes the ATP-dependent amination of UTP to CTP with either L-glutamine or ammonia as the source of nitrogen. Constitutes the rate-limiting enzyme in the synthesis of cytosine nucleotides.^[1] ^[2]

Publication Abstract from PubMed

Many enzymes assemble into defined oligomers, providing a mechanism for cooperatively regulating activity. Recent studies have described a mode of regulation in which enzyme activity is modulated by polymerization into large-scale filaments. Here we describe an ultrasensitive form of polymerization-based regulation employed by human CTP synthase 2 (CTPS2). Cryo-EM structures reveal that CTPS2 filaments dynamically switch between active and inactive forms in response to changes in substrate and product levels. Linking the conformational state of many CTPS2 subunits in a filament results in highly cooperative regulation, greatly exceeding the limits of cooperativity for the CTPS2 tetramer alone. The structures reveal a link between conformation and control of ammonia channeling between the enzyme's active sites, and explain differences in regulation of human CTPS isoforms. This filament-based mechanism of enhanced cooperativity demonstrates how the widespread phenomenon of enzyme polymerization can be adapted to achieve different regulatory outcomes.

Coupled structural transitions enable highly cooperative regulation of human CTPS2 filaments.,Lynch EM, Kollman JM Nat Struct Mol Biol. 2019 Dec 23. pii: 10.1038/s41594-019-0352-5. doi:, 10.1038/s41594-019-0352-5. PMID:31873303^[3]

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

References

↑ van Kuilenburg AB, Meinsma R, Vreken P, Waterham HR, van Gennip AH. Identification of a cDNA encoding an isoform of human CTP synthetase. Biochim Biophys Acta. 2000 Jul 24;1492(2-3):548-52. PMID:10899599
↑ 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
↑ Lynch EM, Kollman JM. Coupled structural transitions enable highly cooperative regulation of human CTPS2 filaments. Nat Struct Mol Biol. 2019 Dec 23. pii: 10.1038/s41594-019-0352-5. doi:, 10.1038/s41594-019-0352-5. PMID:31873303 doi:http://dx.doi.org/10.1038/s41594-019-0352-5

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6pk4"

@@ Line 3: / Line 3: @@
 <SX load='6pk4' size='340' side='right' viewer='molstar' caption='[[6pk4]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6pk4]] 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=6PK4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PK4 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6pk4]] 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=6PK4 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6PK4 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=UTP:URIDINE+5-TRIPHOSPHATE'>UTP</scene></td></tr>
+</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">CTPS2 ([http://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'>[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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6pk4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pk4 OCA], [http://pdbe.org/6pk4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pk4 RCSB], [http://www.ebi.ac.uk/pdbsum/6pk4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pk4 ProSAT]</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=6pk4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pk4 OCA], [http://pdbe.org/6pk4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pk4 RCSB], [http://www.ebi.ac.uk/pdbsum/6pk4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pk4 ProSAT]</span></td></tr>
 </table>
 == Function ==

6pk4

From Proteopedia

Revision as of 04:29, 11 April 2020

cryoEM structure of the substrate-bound human CTP synthase 2 filament

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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