7zeh

From Proteopedia

(Difference between revisions)

Revision as of 13:31, 1 February 2024

Human cytosolic 5' nucleotidase IIIB in complex with 3,4-diF-Bn7Guanine

Structural highlights

7zeh is a 4 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 1.5Å
Ligands:	, , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

5NT3B_HUMAN Specifically hydrolyzes 7-methylguanosine monophosphate (m(7)GMP) to 7-methylguanosine and inorganic phosphate (PubMed:23223233, PubMed:24603684). The specific activity for m(7)GMP may protect cells against undesired salvage of m(7)GMP and its incorporation into nucleic acids (PubMed:23223233). Also has weak activity for CMP (PubMed:23223233, PubMed:24603684). UMP and purine nucleotides are poor substrates (PubMed:23223233).^[1] ^[2]

Publication Abstract from PubMed

Cytosolic nucleotidases (cNs) catalyze dephosphorylation of nucleoside 5'-monophosphates and thereby contribute to the regulation of nucleotide levels in cells. cNs have also been shown to dephosphorylate several therapeutically relevant nucleotide analogues. cN-IIIB has shown in vitro a distinctive activity towards 7-mehtylguanosine monophosphate (m(7)GMP), which is one key metabolites of mRNA cap. Consequently, it has been proposed that cN-IIIB participates in mRNA cap turnover and prevents undesired accumulation and salvage of m(7)GMP. Here, we sought to develop molecular tools enabling more advanced studies on the cellular role of cN-IIIB. To that end, we performed substrate and inhibitor property profiling using a library of 41 substrate analogs. The most potent hit compounds (identified among m(7)GMP analogs) were used as a starting point for structure-activity relationship studies. As a result, we identified several 7-benzylguanosine 5'-monophosphate (Bn(7)GMP) derivatives as potent, unhydrolyzable cN-IIIB inhibitors. The mechanism of inhibition was elucidated using X-ray crystallography and molecular docking. Finally, we showed that compounds that potently inhibit recombinant cN-IIIB have the ability to inhibit m(7)GMP decay in cell lysates.

Substrate-Based Design of Cytosolic Nucleotidase IIIB Inhibitors and Structural Insights into Inhibition Mechanism.,Kubacka D, Kozarski M, Baranowski MR, Wojcik R, Panecka-Hofman J, Strzelecka D, Basquin J, Jemielity J, Kowalska J Pharmaceuticals (Basel). 2022 Apr 29;15(5). pii: ph15050554. doi:, 10.3390/ph15050554. PMID:35631380^[3]

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

References

↑ Buschmann J, Moritz B, Jeske M, Lilie H, Schierhorn A, Wahle E. Identification of Drosophila and human 7-methyl GMP-specific nucleotidases. J Biol Chem. 2013 Jan 25;288(4):2441-51. doi: 10.1074/jbc.M112.426700. Epub 2012 , Dec 5. PMID:23223233 doi:http://dx.doi.org/10.1074/jbc.M112.426700
↑ Monecke T, Buschmann J, Neumann P, Wahle E, Ficner R. Crystal Structures of the Novel Cytosolic 5'-Nucleotidase IIIB Explain Its Preference for m7GMP. PLoS One. 2014 Mar 6;9(3):e90915. doi: 10.1371/journal.pone.0090915. eCollection , 2014. PMID:24603684 doi:http://dx.doi.org/10.1371/journal.pone.0090915
↑ Kubacka D, Kozarski M, Baranowski MR, Wojcik R, Panecka-Hofman J, Strzelecka D, Basquin J, Jemielity J, Kowalska J. Substrate-Based Design of Cytosolic Nucleotidase IIIB Inhibitors and Structural Insights into Inhibition Mechanism. Pharmaceuticals (Basel). 2022 Apr 29;15(5). pii: ph15050554. doi:, 10.3390/ph15050554. PMID:35631380 doi:http://dx.doi.org/10.3390/ph15050554

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/7zeh"

@@ Line 3: / Line 3: @@
 <StructureSection load='7zeh' size='340' side='right'caption='[[7zeh]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7zeh]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ZEH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZEH FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7zeh]] is a 4 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=7ZEH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZEH FirstGlance]. <br>
-</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=IPQ:N7-(3,4-difluorobenzyl)+guanine'>IPQ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=RBL:D-RIBULOSE'>RBL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.5&#8491;</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=IPQ:N7-(3,4-difluorobenzyl)+guanine'>IPQ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=RBL:D-RIBULOSE'>RBL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=7zeh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zeh OCA], [https://pdbe.org/7zeh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zeh RCSB], [https://www.ebi.ac.uk/pdbsum/7zeh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zeh ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/5NT3B_HUMAN 5NT3B_HUMAN]] Specifically hydrolyzes 7-methylguanosine monophosphate (m(7)GMP) to 7-methylguanosine and inorganic phosphate (PubMed:23223233, PubMed:24603684). The specific activity for m(7)GMP may protect cells against undesired salvage of m(7)GMP and its incorporation into nucleic acids (PubMed:23223233). Also has weak activity for CMP (PubMed:23223233, PubMed:24603684). UMP and purine nucleotides are poor substrates (PubMed:23223233).<ref>PMID:23223233</ref> <ref>PMID:24603684</ref>
+[https://www.uniprot.org/uniprot/5NT3B_HUMAN 5NT3B_HUMAN] Specifically hydrolyzes 7-methylguanosine monophosphate (m(7)GMP) to 7-methylguanosine and inorganic phosphate (PubMed:23223233, PubMed:24603684). The specific activity for m(7)GMP may protect cells against undesired salvage of m(7)GMP and its incorporation into nucleic acids (PubMed:23223233). Also has weak activity for CMP (PubMed:23223233, PubMed:24603684). UMP and purine nucleotides are poor substrates (PubMed:23223233).<ref>PMID:23223233</ref> <ref>PMID:24603684</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Baranowski, M R]]
+[[Category: Baranowski MR]]
-[[Category: Basquin, J]]
+[[Category: Basquin J]]
-[[Category: Jemielity, J]]
+[[Category: Jemielity J]]
-[[Category: Kowalska, J]]
+[[Category: Kowalska J]]
-[[Category: Kozarski, M]]
+[[Category: Kozarski M]]
-[[Category: Kubacka, D]]
+[[Category: Kubacka D]]
-[[Category: Wojcik, R]]
+[[Category: Wojcik R]]
-[[Category: Cytosolic 5' nucleotidase]]
-[[Category: Hydrolase]]
-[[Category: Mrna cap degradation]]
-[[Category: N7 methylguanosine monophosphate dephosphorylation]]

7zeh

From Proteopedia

Revision as of 13:31, 1 February 2024

Human cytosolic 5' nucleotidase IIIB in complex with 3,4-diF-Bn7Guanine

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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