3MCV

Structure of PTR1 from Trypanosoma brucei in ternary complex with 2,4-diamino-5-[2-(2,5-dimethoxyphenyl)ethyl]thieno[2,3-d]-pyrimidine and NADP+

PDB DOI: https://doi.org/10.2210/pdb3MCV/pdb

Classification: OXIDOREDUCTASE
Organism(s): Trypanosoma brucei brucei
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2010-03-29 Released: 2010-06-02
Deposition Author(s): Tulloch, L.B., Hunter, W.N.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.70 ?
R-Value Free: 0.167
R-Value Work: 0.135
R-Value Observed: 0.137

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.2 of the entry. See complete history.

Literature

High-resolution structures of Trypanosoma brucei pteridine reductase ligand complexes inform on the placement of new molecular entities in the active site of a potential drug target.

Dawson, A., Tulloch, L.B., Barrack, K.L., Hunter, W.N.

(2010) Acta Crystallogr D Biol Crystallogr 66: 1334-1340

PubMed: 21123874 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1107/S0907444910040886
Primary Citation of Related Structures:
2X9G, 2X9N, 2X9V, 3MCV

PubMed Abstract:
Pteridine reductase (PTR1) is a potential target for drug development against parasitic Trypanosoma and Leishmania species. These protozoa cause serious diseases for which current therapies are inadequate. High-resolution structures have been determined, using data between 1.6 and 1.1?? resolution, of T. brucei PTR1 in complex with pemetrexed, trimetrexate, cyromazine and a 2,4-diaminopyrimidine derivative. The structures provide insight into the interactions formed by new molecular entities in the enzyme active site with ligands that represent lead compounds for structure-based inhibitor development and to support early-stage drug discovery.

Organizational Affiliation

Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD15EH, Scotland.

Macromolecule Content

Total Structure Weight: 127.21 kDa
Atom Count: 8,712
Modelled Residue Count: 1,000
Deposited Residue Count: 1,152
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Pteridine reductase	A, B, C, D	288	Trypanosoma brucei brucei	Mutation(s): 0 Gene Names: PTR1 EC: 1.5.1.33
UniProt
Find proteins for O76290 (Trypanosoma brucei brucei) Explore O76290 Go to UniProtKB: O76290
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	O76290
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
NAP Query on NAP Download Ideal Coordinates CCD File SDF format, chain H [auth B] SDF format, chain E [auth A] SDF format, chain L [auth C] SDF format, chain N [auth D] MOL2 format, chain H [auth B] MOL2 format, chain E [auth A] MOL2 format, chain L [auth C] MOL2 format, chain N [auth D] mmCIF format, chain H [auth B] mmCIF format, chain E [auth A] mmCIF format, chain L [auth C] mmCIF format, chain N [auth D]	E [auth A], H [auth B], L [auth C], N [auth D]	NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE C₂₁ H₂₈ N₇ O₁₇ P₃ XJLXINKUBYWONI-NNYOXOHSSA-N		Interactions Focus chain E [auth A] Focus chain H [auth B] Focus chain L [auth C] Focus chain N [auth D] Interactions & Density Focus chain E [auth A] Focus chain H [auth B] Focus chain L [auth C] Focus chain N [auth D]
MCV Query on MCV Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain I [auth B] SDF format, chain M [auth C] SDF format, chain O [auth D] MOL2 format, chain F [auth A] MOL2 format, chain I [auth B] MOL2 format, chain M [auth C] MOL2 format, chain O [auth D] mmCIF format, chain F [auth A] mmCIF format, chain I [auth B] mmCIF format, chain M [auth C] mmCIF format, chain O [auth D]	F [auth A], I [auth B], M [auth C], O [auth D]	5-[2-(2,5-dimethoxyphenyl)ethyl]thieno[2,3-d]pyrimidine-2,4-diamine C₁₆ H₁₈ N₄ O₂ S XJFDLPAAAIBWID-UHFFFAOYSA-N		Interactions Focus chain F [auth A] Focus chain I [auth B] Focus chain M [auth C] Focus chain O [auth D] Interactions & Density Focus chain F [auth A] Focus chain I [auth B] Focus chain M [auth C] Focus chain O [auth D]
ACT Query on ACT Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain J [auth B] SDF format, chain K [auth B] SDF format, chain P [auth D] MOL2 format, chain G [auth A] MOL2 format, chain J [auth B] MOL2 format, chain K [auth B] MOL2 format, chain P [auth D] mmCIF format, chain G [auth A] mmCIF format, chain J [auth B] mmCIF format, chain K [auth B] mmCIF format, chain P [auth D]	G [auth A], J [auth B], K [auth B], P [auth D]	ACETATE ION C₂ H₃ O₂ QTBSBXVTEAMEQO-UHFFFAOYSA-M		Interactions Focus chain G [auth A] Focus chain J [auth B] Focus chain K [auth B] Focus chain P [auth D] Interactions & Density Focus chain G [auth A] Focus chain J [auth B] Focus chain K [auth B] Focus chain P [auth D]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.70 ?
R-Value Free: 0.167
R-Value Work: 0.135
R-Value Observed: 0.137
Space Group: P 1 2₁ 1

Unit Cell:

Length ( ? )	Angle ( ? )
a = 74.502	α = 90
b = 89.819	β = 115.49
c = 82.26	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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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2010-06-02

Deposition Author(s):

Tulloch, L.B.

Hunter, W.N.

Revision History (Full details and data files)

Version 1.0: 2010-06-02
Type: Initial release
Version 1.1: 2011-07-13
Changes: Advisory, Refinement description, Version format compliance
Version 1.2: 2024-02-21
Changes: Data collection, Database references, Derived calculations

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3MCV

Structure of PTR1 from Trypanosoma brucei in ternary complex with 2,4-diamino-5-[2-(2,5-dimethoxyphenyl)ethyl]thieno[2,3-d]-pyrimidine and NADP+

High-resolution structures of Trypanosoma brucei pteridine reductase ligand complexes inform on the placement of new molecular entities in the active site of a potential drug target.

Entity ID: 1

UniProt

Entity Groups

Sequence Annotations

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Experimental Data

Structure Validation

Ligand Structure Quality Assessment

Deposition Data

Revision History (Full details and data files)