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4p5e

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Revision as of 12:42, 1 February 2023

CRYSTAL STRUCTURE OF HUMAN DNPH1 (RCL) WITH 6-NAPHTHYL-PURINE-RIBOSIDE-MONOPHOSPHATE

Structural highlights

4p5e is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DNPH1_HUMAN Catalyzes the cleavage of the N-glycosidic bond of deoxyribonucleoside 5'-monophosphates to yield deoxyribose 5-phosphate and a purine or pyrimidine base. Deoxyribonucleoside 5'-monophosphates containing purine bases are preferred to those containing pyrimidine bases (By similarity).[HAMAP-Rule:MF_03036]

Publication Abstract from PubMed

The 2'-deoxynucleoside 5'-phosphate N-hydrolase 1 (DNPH1) has been proposed as a new molecular target for cancer treatment. Here, we describe the synthesis of a series of novel 6-aryl- and 6-heteroarylpurine riboside 5'-monophosphates via Suzuki-Miyaura cross-coupling reactions, and their ability to inhibit recombinant rat and human DNPH1. Enzymatic inhibition studies revealed competitive inhibitors in the low micromolar range. Crystal structures of human and rat DNPH1 in complex with one nucleotide from this series, the 6-naphthylpurine derivative, provided detailed structural information, in particular regarding the possible conformations of a long and flexible loop wrapping around the large hydrophobic substituent. Taking advantage of these high-resolution structures, we performed virtual docking studies in order to evaluate enzyme-inhibitor interactions for the whole compound series. Among the synthesized compounds, several molecules exhibited significant in vitro cytotoxicity against human colon cancer (HCT15, HCT116) and human promyelocytic leukemia (HL60) cell lines with IC50 values in the low micromolar range, which correlated with in vitro DNPH1 inhibitory potency.

6-(Hetero)Arylpurine nucleotides as inhibitors of the oncogenic target DNPH1: Synthesis, structural studies and cytotoxic activities.,Amiable C, Paoletti J, Haouz A, Padilla A, Labesse G, Kaminski PA, Pochet S Eur J Med Chem. 2014 Aug 1;85C:418-437. doi: 10.1016/j.ejmech.2014.07.110. PMID:25108359^[1]

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

References

↑ Amiable C, Paoletti J, Haouz A, Padilla A, Labesse G, Kaminski PA, Pochet S. 6-(Hetero)Arylpurine nucleotides as inhibitors of the oncogenic target DNPH1: Synthesis, structural studies and cytotoxic activities. Eur J Med Chem. 2014 Aug 1;85C:418-437. doi: 10.1016/j.ejmech.2014.07.110. PMID:25108359 doi:http://dx.doi.org/10.1016/j.ejmech.2014.07.110

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/4p5e"

Categories: Homo sapiens | Large Structures | Kaminski PA | Labesse G | Padilla A

@@ Line 3: / Line 3: @@
 <StructureSection load='4p5e' size='340' side='right'caption='[[4p5e]], [[Resolution|resolution]] 1.35&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4p5e]] 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=4P5E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4P5E FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4p5e]] is a 2 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=4P5E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4P5E FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=N6P:6-(NAPHTHALEN-2-YL)-9-(5-O-PHOSPHONO-BETA-D-RIBOFURANOSYL)-9H-PURINE'>N6P</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=N6P:6-(NAPHTHALEN-2-YL)-9-(5-O-PHOSPHONO-BETA-D-RIBOFURANOSYL)-9H-PURINE'>N6P</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4fyi|4fyi]], [[4p5d|4p5d]]</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=4p5e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p5e OCA], [https://pdbe.org/4p5e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4p5e RCSB], [https://www.ebi.ac.uk/pdbsum/4p5e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4p5e ProSAT]</span></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DNPH1, C6orf108, RCL ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4p5e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p5e OCA], [http://pdbe.org/4p5e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4p5e RCSB], [http://www.ebi.ac.uk/pdbsum/4p5e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4p5e ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/DNPH1_HUMAN DNPH1_HUMAN]] Catalyzes the cleavage of the N-glycosidic bond of deoxyribonucleoside 5'-monophosphates to yield deoxyribose 5-phosphate and a purine or pyrimidine base. Deoxyribonucleoside 5'-monophosphates containing purine bases are preferred to those containing pyrimidine bases (By similarity).[HAMAP-Rule:MF_03036]
+[https://www.uniprot.org/uniprot/DNPH1_HUMAN DNPH1_HUMAN] Catalyzes the cleavage of the N-glycosidic bond of deoxyribonucleoside 5'-monophosphates to yield deoxyribose 5-phosphate and a purine or pyrimidine base. Deoxyribonucleoside 5'-monophosphates containing purine bases are preferred to those containing pyrimidine bases (By similarity).[HAMAP-Rule:MF_03036]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 22: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Kaminski, P A]]
+[[Category: Kaminski PA]]
-[[Category: Labesse, G]]
+[[Category: Labesse G]]
-[[Category: Padilla, A]]
+[[Category: Padilla A]]
-[[Category: Dnph1]]
-[[Category: Hydrolase]]
-[[Category: Inhibitor]]
-[[Category: Rcl]]
-[[Category: Rossmann fold]]

4p5e

From Proteopedia

Revision as of 12:42, 1 February 2023

CRYSTAL STRUCTURE OF HUMAN DNPH1 (RCL) WITH 6-NAPHTHYL-PURINE-RIBOSIDE-MONOPHOSPHATE

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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