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5l50

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Revision as of 06:44, 5 August 2020

Crystal structure of enzyme in purine metabolism

Structural highlights

5l50 is a 1 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

BACKGROUND: Relapsed acute lymphoblastic leukemia (ALL) is one of the main causes of mortality in childhood malignancies. Previous genetic studies demonstrated that chemoresistant ALL is driven by activating mutations in NT5C2, the gene encoding cytosolic 5 -nucleotidase (cN-II). However, molecular mechanisms underlying this hyperactivation are still unknown. Here, we present kinetic and structural properties of cN-II variants that represent 75 % of mutated alleles in patients who experience relapsed ALL (R367Q, R238W and L375F). RESULTS: Enzyme kinetics measurements revealed that the mutants are consitutively active without need for allosteric activators. This shows that hyperactivity is not caused by a direct catalytic effect but rather by misregulation of cN-II. X-ray crystallography combined with mass spectrometry-based techniques demonstrated that this misregulation is driven by structural modulation of the oligomeric interface within the cN-II homotetrameric assembly. These specific conformational changes are shared between the studied variants, despite the relatively random spatial distribution of the mutations. CONCLUSIONS: These findings define a common molecular mechanism for cN-II hyperactivity, which provides a solid basis for targeted therapy of leukemia. Our study highlights the cN-II oligomerization interface as an attractive pharmacological target.

Oligomeric interface modulation causes misregulation of purine 5 -nucleotidase in relapsed leukemia.,Hnizda A, Skerlova J, Fabry M, Pachl P, Sinalova M, Vrzal L, Man P, Novak P, Rezacova P, Veverka V BMC Biol. 2016 Oct 19;14(1):91. PMID:27756303^[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
↑ Hnizda A, Skerlova J, Fabry M, Pachl P, Sinalova M, Vrzal L, Man P, Novak P, Rezacova P, Veverka V. Oligomeric interface modulation causes misregulation of purine 5 -nucleotidase in relapsed leukemia. BMC Biol. 2016 Oct 19;14(1):91. PMID:27756303 doi:http://dx.doi.org/10.1186/s12915-016-0313-y

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/5l50"

@@ Line 1: / Line 1: @@
 ==Crystal structure of enzyme in purine metabolism==
-<StructureSection load='5l50' size='340' side='right' caption='[[5l50]], [[Resolution|resolution]] 1.64&Aring;' scene=''>
+<StructureSection load='5l50' size='340' side='right'caption='[[5l50]], [[Resolution|resolution]] 1.64&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5l50]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5L50 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5L50 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5l50]] 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=5L50 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5L50 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
+</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='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='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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5l50 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l50 OCA], [http://pdbe.org/5l50 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5l50 RCSB], [http://www.ebi.ac.uk/pdbsum/5l50 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5l50 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=5l50 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l50 OCA], [http://pdbe.org/5l50 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5l50 RCSB], [http://www.ebi.ac.uk/pdbsum/5l50 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5l50 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 26: / Line 27: @@
 </StructureSection>
 [[Category: 5'-nucleotidase]]
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Hnizda, A]]
 [[Category: Pachl, P]]

5l50

From Proteopedia

Revision as of 06:44, 5 August 2020

Crystal structure of enzyme in purine metabolism

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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