4KXM

Crystal structure of DNPH1 (RCL) WITH N6-ISOPENTENYL-AMP

PDB DOI: https://doi.org/10.2210/pdb4KXM/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: 2.24 Å
R-Value Free: 0.227
R-Value Work: 0.174
R-Value Observed: 0.176

Starting Model: experimental
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Ligand Structure Quality Assessment

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: 70.36 kDa
Atom Count: 4,457
Modelled Residue Count: 525
Deposited Residue Count: 608
Unique protein chains: 1

Macromolecules

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(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
6IA Query on 6IA 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]	N6-ISOPENTENYL-ADENOSINE-5'-MONOPHOSPHATE C₁₅ H₂₄ N₅ O₇ P GZJXCRHEMLAMRA-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: 2.24 Å
R-Value Free: 0.227
R-Value Work: 0.174
R-Value Observed: 0.176
Space Group: P 1 2₁ 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 32.146	α = 90
b = 96.568	β = 101.58
c = 79.034	γ = 90

Software Package:

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

Structure Validation

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Ligand Structure Quality Assessment

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