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5g1n

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Revision as of 06:34, 13 May 2020

Aspartate transcarbamoylase domain of human CAD bound to PALA

Structural highlights

5g1n is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	5g1o, 5g1p
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PYR1_HUMAN] This protein is a "fusion" protein encoding four enzymatic activities of the pyrimidine pathway (GATase, CPSase, ATCase and DHOase).

Publication Abstract from PubMed

CAD, the multienzymatic protein that initiates and controls de novo synthesis of pyrimidines in animals, associates through its aspartate transcarbamoylase (ATCase) domain into particles of 1.5 MDa. Despite numerous structures of prokaryotic ATCases, we lack structural information on the ATCase domain of CAD. Here, we report the structure and functional characterization of human ATCase, confirming the overall similarity with bacterial homologs. Unexpectedly, human ATCase exhibits cooperativity effects that reduce the affinity for the anti-tumoral drug PALA. Combining structural, mutagenic, and biochemical analysis, we identified key elements for the necessary regulation and transmission of conformational changes leading to cooperativity between subunits. Mutation of one of these elements, R2024, was recently found to cause the first non-lethal CAD deficit. We reproduced this mutation in human ATCase and measured its effect, demonstrating that this arginine is part of a molecular switch that regulates the equilibrium between low- and high-affinity states for the ligands.

Structure and Functional Characterization of Human Aspartate Transcarbamoylase, the Target of the Anti-tumoral Drug PALA.,Ruiz-Ramos A, Velazquez-Campoy A, Grande-Garcia A, Moreno-Morcillo M, Ramon-Maiques S Structure. 2016 May 31. pii: S0969-2126(16)30079-X. doi:, 10.1016/j.str.2016.05.001. PMID:27265852^[1]

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

References

↑ Ruiz-Ramos A, Velazquez-Campoy A, Grande-Garcia A, Moreno-Morcillo M, Ramon-Maiques S. Structure and Functional Characterization of Human Aspartate Transcarbamoylase, the Target of the Anti-tumoral Drug PALA. Structure. 2016 May 31. pii: S0969-2126(16)30079-X. doi:, 10.1016/j.str.2016.05.001. PMID:27265852 doi:http://dx.doi.org/10.1016/j.str.2016.05.001

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/5g1n"

@@ Line 1: / Line 1: @@
 ==Aspartate transcarbamoylase domain of human CAD bound to PALA==
-<StructureSection load='5g1n' size='340' side='right' caption='[[5g1n]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+<StructureSection load='5g1n' size='340' side='right'caption='[[5g1n]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5g1n]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5G1N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5G1N FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5g1n]] is a 6 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=5G1N OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5G1N FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PAL:N-(PHOSPHONACETYL)-L-ASPARTIC+ACID'>PAL</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PAL:N-(PHOSPHONACETYL)-L-ASPARTIC+ACID'>PAL</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5g1o|5g1o]], [[5g1p|5g1p]]</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=5g1n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5g1n OCA], [http://pdbe.org/5g1n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5g1n RCSB], [http://www.ebi.ac.uk/pdbsum/5g1n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5g1n 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=5g1n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5g1n OCA], [http://pdbe.org/5g1n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5g1n RCSB], [http://www.ebi.ac.uk/pdbsum/5g1n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5g1n ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 23: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Grande-Garcia, A]]
 [[Category: Moreno-Morcillo, M D]]

5g1n

From Proteopedia

Revision as of 06:34, 13 May 2020

Aspartate transcarbamoylase domain of human CAD bound to PALA

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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