This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

2xcx

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

Crystal structure of the apoform of the D52N variant of cytosolic 5'- nucleotidase II

Structural highlights

2xcx 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 2.3Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

5NTC_HUMAN Autosomal recessive spastic paraplegia type 45. The disease is caused by mutations affecting the gene represented in this entry.^[1]

Function

5NTC_HUMAN May have a critical role in the maintenance of a constant composition of intracellular purine/pyrimidine nucleotides in cooperation with other nucleotidases. Preferentially hydrolyzes inosine 5'-monophosphate (IMP) and other purine nucleotides.

Publication Abstract from PubMed

Cytosolic 5'-nucleotidase II (cN-II) catalyzes the dephosphorylation of 6-hydroxypurine nucleoside 5'-monophosphates and participates in the regulation of purine nucleotide pools within the cell. It interferes with the phosphorylation-dependent activation of nucleoside analogues used in the treatment of cancer and viral diseases. It is allosterically activated by a number of phosphate-containing cellular metabolites such as ATP, diadenosine polyphosphates, and 2,3-bisphosphoglycerate, which couple its activity with the metabolic state of the cell. We present seven high-resolution structures of human cN-II, including a ligand-free form and complexes with various substrates and effectors. These structures reveal the structural basis for the allosteric activation of cN-II, uncovering a mechanism where an effector-induced disorder-to-order transition generates rearrangements within the catalytic site and the subsequent coordination of the catalytically essential magnesium. Central to the activation is the large transition of the catalytically essential Asp356. This study also provides the structural basis for the substrate specificity of cN-II, where Arg202, Asp206, and Phe157 seem to be important residues for purine/pyrimidine selectivity. These structures provide a comprehensive structural basis for the design of cN-II inhibitors. They also contribute to the understanding of how the nucleotide salvage pathway is regulated at a molecular level.

Structural Basis for the Allosteric Regulation and Substrate Recognition of Human Cytosolic 5'-Nucleotidase II.,Wallden K, Nordlund P J Mol Biol. 2011 May 13;408(4):684-96. Epub 2011 Mar 17. PMID:21396942^[2]

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

References

↑ Novarino G, Fenstermaker AG, Zaki MS, Hofree M, Silhavy JL, Heiberg AD, Abdellateef M, Rosti B, Scott E, Mansour L, Masri A, Kayserili H, Al-Aama JY, Abdel-Salam GM, Karminejad A, Kara M, Kara B, Bozorgmehri B, Ben-Omran T, Mojahedi F, Mahmoud IG, Bouslam N, Bouhouche A, Benomar A, Hanein S, Raymond L, Forlani S, Mascaro M, Selim L, Shehata N, Al-Allawi N, Bindu PS, Azam M, Gunel M, Caglayan A, Bilguvar K, Tolun A, Issa MY, Schroth J, Spencer EG, Rosti RO, Akizu N, Vaux KK, Johansen A, Koh AA, Megahed H, Durr A, Brice A, Stevanin G, Gabriel SB, Ideker T, Gleeson JG. Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. Science. 2014 Jan 31;343(6170):506-11. doi: 10.1126/science.1247363. PMID:24482476 doi:http://dx.doi.org/10.1126/science.1247363
↑ Wallden K, Nordlund P. Structural Basis for the Allosteric Regulation and Substrate Recognition of Human Cytosolic 5'-Nucleotidase II. J Mol Biol. 2011 May 13;408(4):684-96. Epub 2011 Mar 17. PMID:21396942 doi:10.1016/j.jmb.2011.02.059

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/2xcx"

Categories: Homo sapiens | Large Structures | Nordlund P | Wallden K

@@ Line 3: / Line 3: @@
 <StructureSection load='2xcx' size='340' side='right'caption='[[2xcx]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2xcx]] 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=2XCX OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2XCX FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2xcx]] 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=2XCX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XCX FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2.3&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2xcv|2xcv]], [[2jc9|2jc9]], [[2xje|2xje]], [[2xjd|2xjd]], [[2xjf|2xjf]], [[2j2c|2j2c]], [[2xjb|2xjb]], [[2jcm|2jcm]], [[2xjc|2xjc]], [[2xcw|2xcw]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/5'-nucleotidase 5'-nucleotidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.5 3.1.3.5] </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=2xcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xcx OCA], [https://pdbe.org/2xcx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xcx RCSB], [https://www.ebi.ac.uk/pdbsum/2xcx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xcx 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=2xcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xcx OCA], [http://pdbe.org/2xcx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2xcx RCSB], [http://www.ebi.ac.uk/pdbsum/2xcx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2xcx ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/5NTC_HUMAN 5NTC_HUMAN]] Autosomal recessive spastic paraplegia type 45. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:24482476</ref>
+[https://www.uniprot.org/uniprot/5NTC_HUMAN 5NTC_HUMAN] Autosomal recessive spastic paraplegia type 45. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:24482476</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/5NTC_HUMAN 5NTC_HUMAN]] May have a critical role in the maintenance of a constant composition of intracellular purine/pyrimidine nucleotides in cooperation with other nucleotidases. Preferentially hydrolyzes inosine 5'-monophosphate (IMP) and other purine nucleotides.
+[https://www.uniprot.org/uniprot/5NTC_HUMAN 5NTC_HUMAN] May have a critical role in the maintenance of a constant composition of intracellular purine/pyrimidine nucleotides in cooperation with other nucleotidases. Preferentially hydrolyzes inosine 5'-monophosphate (IMP) and other purine nucleotides.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 26: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: 5'-nucleotidase]]
+[[Category: Homo sapiens]]
-[[Category: Human]]
 [[Category: Large Structures]]
-[[Category: Nordlund, P]]
+[[Category: Nordlund P]]
-[[Category: Wallden, K]]
+[[Category: Wallden K]]
-[[Category: Cn-ii]]
-[[Category: Gmp-imp specific nucleotidase]]
-[[Category: High km 5-prime nucleotidase]]
-[[Category: Hydrolase]]
-[[Category: Metal-binding]]
-[[Category: Nt5c2]]
-[[Category: Nucleotide metabolism]]
-[[Category: Nucleotide-binding]]

2xcx

From Proteopedia

Current revision

Crystal structure of the apoform of the D52N variant of cytosolic 5'- nucleotidase II

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox