4KXN

Crystal structure of DNPH1 (RCL) with kinetine riboside monophosphate

PDB DOI: https://doi.org/10.2210/pdb4KXN/pdb

Classification: HYDROLASE
Organism(s): Rattus norvegicus
Expression System: Escherichia coli
Mutation(s): Yes

Deposited: 2013-05-27 Released: 2014-02-05
Deposition Author(s): Padilla, A., Labesse, G., Kaminski, P.A.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.90 Å
R-Value Free: 0.286
R-Value Work: 0.232
R-Value Observed: 0.235

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

This is version 1.1 of the entry. See complete history.

Literature

N (6)-substituted AMPs inhibit mammalian deoxynucleotide N-hydrolase DNPH1.

Amiable, C., Pochet, S., Padilla, A., Labesse, G., Kaminski, P.A.

(2013) PLoS One 8: e80755-e80755

PubMed: 24260472 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1371/journal.pone.0080755
Primary Citation of Related Structures:
4KXL, 4KXM, 4KXN

PubMed Abstract:
The gene dnph1 (or rcl) encodes a hydrolase that cleaves the 2'-deoxyribonucleoside 5'-monophosphate (dNMP) N-glycosidic bond to yield a free nucleobase and 2-deoxyribose 5-phosphate. Recently, the crystal structure of rat DNPH1, a potential target for anti-cancer therapies, suggested that various analogs of AMP may inhibit this enzyme. From this result, we asked whether N (6)-substituted AMPs, and among them, cytotoxic cytokinin riboside 5'-monophosphates, may inhibit DNPH1. Here, we characterized the structural and thermodynamic aspects of the interactions of these various analogs with DNPH1. Our results indicate that DNPH1 is inhibited by cytotoxic cytokinins at concentrations that inhibit cell growth.

Organizational Affiliation

Institut Pasteur, Unité de Chimie et Biocatalyse, Paris, France ; CNRS, UMR3523, Paris, France ; Université Paris Descartes Sorbonne Paris Cité, Paris, France.

Macromolecule Content

Total Structure Weight: 70.4 kDa
Atom Count: 4,419
Modelled Residue Count: 513
Deposited Residue Count: 608
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
2'-deoxynucleoside 5'-phosphate N-hydrolase 1	A, B, C, D	152	Rattus norvegicus	Mutation(s): 1 Gene Names: Dnph1, Rcl EC: 3.2.2
UniProt
Find proteins for O35820 (Rattus norvegicus) Explore O35820 Go to UniProtKB: O35820
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	O35820
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 1 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
6K6 Query on 6K6 Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain F [auth B] SDF format, chain G [auth C] SDF format, chain H [auth D] MOL2 format, chain E [auth A] MOL2 format, chain F [auth B] MOL2 format, chain G [auth C] MOL2 format, chain H [auth D] mmCIF format, chain E [auth A] mmCIF format, chain F [auth B] mmCIF format, chain G [auth C] mmCIF format, chain H [auth D]	E [auth A], F [auth B], G [auth C], H [auth D]	N-(furan-2-ylmethyl)adenosine 5'-(dihydrogen phosphate) C₁₅ H₁₈ N₅ O₈ P WDFCXEWULSQTFC-SDBHATRESA-N		Interactions Focus chain E [auth A] Focus chain F [auth B] Focus chain G [auth C] Focus chain H [auth D] Interactions & Density Focus chain E [auth A] Focus chain F [auth B] Focus chain G [auth C] Focus chain H [auth D]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.90 Å
R-Value Free: 0.286
R-Value Work: 0.232
R-Value Observed: 0.235
Space Group: P 1 2₁ 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 32.238	α = 90
b = 95.449	β = 101.56
c = 79.288	γ = 90

Software Package:

Software Name	Purpose
MOSFLM	data reduction
SCALA	data scaling
MOLREP	phasing
REFMAC	refinement
PDB_EXTRACT	data extraction

Structure Validation

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Entry History

Deposition Data

Released Date: 2014-02-05

Deposition Author(s):

Padilla, A.

Labesse, G.

Kaminski, P.A.

Revision History (Full details and data files)

Version 1.0: 2014-02-05
Type: Initial release
Version 1.1: 2023-09-20
Changes: Data collection, Database references, Derived calculations, Refinement description