2h31

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of human PAICS, a bifunctional carboxylase and synthetase in purine biosynthesis

Structural highlights

2h31 is a 1 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 2.8Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PUR6_HUMAN

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

Phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) is an important bifunctional enzyme in de novo purine biosynthesis in vertebrate with both 5-aminoimidazole ribonucleotide carboxylase (AIRc) and 4-(N-succinylcarboxamide)-5-aminoimidazole ribonucleotide synthetase (SAICARs) activities. It becomes an attractive target for rational anticancer drug design, since rapidly dividing cancer cells rely heavily on the purine de novo pathway for synthesis of adenine and guanine, whereas normal cells favor the salvage pathway. Here, we report the crystal structure of human PAICS, the first in the entire PAICS family, at 2.8 A resolution. It revealed that eight PAICS subunits, each composed of distinct AIRc and SAICARs domains, assemble a compact homo-octamer with an octameric-carboxylase core and four symmetric periphery dimers formed by synthetase domains. Based on structural comparison and functional complementation analyses, the active sites of SAICARs and AIRc were identified, including a putative substrate CO(2)-binding site. Furthermore, four symmetry-related, separate tunnel systems in the PAICS octamer were found that connect the active sites of AIRc and SAICARs. This study illustrated the octameric nature of the bifunctional enzyme. Each carboxylase active site is formed by structural elements from three AIRc domains, demonstrating that the octamer structure is essential for the carboxylation activity. Furthermore, the existence of the tunnel system implies a mechanism of intermediate channeling and suggests that the quaternary structure arrangement is crucial for effectively executing the sequential reactions. In addition, this study provides essential structural information for designing PAICS-specific inhibitors for use in cancer chemotherapy.

Octameric structure of the human bifunctional enzyme PAICS in purine biosynthesis.,Li SX, Tong YP, Xie XC, Wang QH, Zhou HN, Han Y, Zhang ZY, Gao W, Li SG, Zhang XC, Bi RC J Mol Biol. 2007 Mar 9;366(5):1603-14. Epub 2006 Dec 16. PMID:17224163^[1]

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

References

↑ Li SX, Tong YP, Xie XC, Wang QH, Zhou HN, Han Y, Zhang ZY, Gao W, Li SG, Zhang XC, Bi RC. Octameric structure of the human bifunctional enzyme PAICS in purine biosynthesis. J Mol Biol. 2007 Mar 9;366(5):1603-14. Epub 2006 Dec 16. PMID:17224163 doi:10.1016/j.jmb.2006.12.027

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2h31"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human PAICS, a bifunctional carboxylase and synthetase in purine biosynthesis==
-<StructureSection load='2h31' size='340' side='right' caption='[[2h31]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+<StructureSection load='2h31' size='340' side='right'caption='[[2h31]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2h31]] is a 1 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=2H31 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2H31 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2h31]] is a 1 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=2H31 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2H31 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CO2:CARBON+DIOXIDE'>CO2</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='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO2:CARBON+DIOXIDE'>CO2</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PAICS, ADE2, AIRC, PAIS ([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=2h31 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h31 OCA], [https://pdbe.org/2h31 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2h31 RCSB], [https://www.ebi.ac.uk/pdbsum/2h31 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2h31 ProSAT]</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=2h31 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h31 OCA], [http://pdbe.org/2h31 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2h31 RCSB], [http://www.ebi.ac.uk/pdbsum/2h31 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2h31 ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/PUR6_HUMAN PUR6_HUMAN]
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 14: / Line 15: @@
   <jmolCheckbox>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h3/2h31_consurf.spt"</scriptWhenChecked>
-    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
@@ Line 28: / Line 29: @@
 </div>
 <div class="pdbe-citations 2h31" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Phosphoribosylaminoimidazole carboxylase 3D structures|Phosphoribosylaminoimidazole carboxylase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Bi, R C]]
+[[Category: Large Structures]]
-[[Category: Li, S G]]
+[[Category: Bi R-C]]
-[[Category: Li, S X]]
+[[Category: Li S-G]]
-[[Category: Tong, Y P]]
+[[Category: Li S-X]]
-[[Category: Xie, X C]]
+[[Category: Tong Y-P]]
-[[Category: Alpha-beta-alpha]]
+[[Category: Xie X-C]]
-[[Category: Ligase]]
-[[Category: Lyase]]

2h31

From Proteopedia

Current revision

Crystal structure of human PAICS, a bifunctional carboxylase and synthetase in purine biosynthesis

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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