6ddq

From Proteopedia

(Difference between revisions)

Revision as of 06:22, 12 May 2022

Crystal structure of the double mutant (R39Q/D52N) of the full-length NT5C2 in the basal state

Structural highlights

6ddq is a 2 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:	NT5C2, NT5B, NT5CP, PNT5 (HUMAN)
Activity:	5'-nucleotidase, with EC number 3.1.3.5
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

Activating mutations in the cytosolic 5'-nucleotidase II gene NT5C2 drive resistance to 6-mercaptopurine in acute lymphoblastic leukemia. Here we demonstrate that constitutively active NT5C2 mutations K359Q and L375F reconfigure the catalytic center for substrate access and catalysis in the absence of allosteric activator. In contrast, most relapse-associated mutations, which involve the arm segment and residues along the surface of the inter-monomeric cavity, disrupt a built-in switch-off mechanism responsible for turning off NT5C2. In addition, we show that the C-terminal acidic tail lost in the Q523X mutation functions to restrain NT5C2 activation. These results uncover dynamic mechanisms of enzyme regulation targeted by chemotherapy resistance-driving NT5C2 mutations, with important implications for the development of NT5C2 inhibitor therapies.

Structure and Mechanisms of NT5C2 Mutations Driving Thiopurine Resistance in Relapsed Lymphoblastic Leukemia.,Dieck CL, Tzoneva G, Forouhar F, Carpenter Z, Ambesi-Impiombato A, Sanchez-Martin M, Kirschner-Schwabe R, Lew S, Seetharaman J, Tong L, Ferrando AA Cancer Cell. 2018 Jul 9;34(1):136-147.e6. doi: 10.1016/j.ccell.2018.06.003. PMID:29990496^[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
↑ Dieck CL, Tzoneva G, Forouhar F, Carpenter Z, Ambesi-Impiombato A, Sanchez-Martin M, Kirschner-Schwabe R, Lew S, Seetharaman J, Tong L, Ferrando AA. Structure and Mechanisms of NT5C2 Mutations Driving Thiopurine Resistance in Relapsed Lymphoblastic Leukemia. Cancer Cell. 2018 Jul 9;34(1):136-147.e6. doi: 10.1016/j.ccell.2018.06.003. PMID:29990496 doi:http://dx.doi.org/10.1016/j.ccell.2018.06.003

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/6ddq"

@@ Line 1: / Line 1: @@
-==Crystal structure of the doublt mutant (R39Q/D52N) of the full-length NT5C2 in the basal state==
+==Crystal structure of the double mutant (R39Q/D52N) of the full-length NT5C2 in the basal state==
 <StructureSection load='6ddq' size='340' side='right'caption='[[6ddq]], [[Resolution|resolution]] 2.31&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6ddq]] is a 2 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=6DDQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DDQ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6ddq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DDQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DDQ 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=PO4:PHOSPHATE+ION'>PO4</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=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NT5C2, NT5B, NT5CP, PNT5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NT5C2, NT5B, NT5CP, PNT5 ([https://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/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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/5'-nucleotidase 5'-nucleotidase], with EC number [https://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ddq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ddq OCA], [http://pdbe.org/6ddq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ddq RCSB], [http://www.ebi.ac.uk/pdbsum/6ddq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ddq ProSAT]</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=6ddq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ddq OCA], [https://pdbe.org/6ddq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ddq RCSB], [https://www.ebi.ac.uk/pdbsum/6ddq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ddq 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 ==

6ddq

From Proteopedia

Revision as of 06:22, 12 May 2022

Crystal structure of the double mutant (R39Q/D52N) of the full-length NT5C2 in the basal state

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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