1W0C

Inhibition of Leishmania major pteridine reductase (PTR1) by 2,4,6-triaminoquinazoline; structure of the NADP ternary complex.

PDB DOI: https://doi.org/10.2210/pdb1W0C/pdb

Classification: OXIDOREDUCTASE
Organism(s): Leishmania major
Expression System: Escherichia coli BL21
Mutation(s): No

Deposited: 2004-06-02 Released: 2004-09-30
Deposition Author(s): Mcluskey, K., Gibellini, F., Carvalho, P., Avery, M., Hunter, W.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.60 ?
R-Value Free: 0.337
R-Value Work: 0.267

Starting Model: experimental
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Literature

Inhibition of Leishmania Major Pteridine Reductase by 2,4,6-Triaminoquinazoline: Structure of the Nadph Ternary Complex

Mcluskey, K., Gibellini, F., Carvalho, P., Avery, M., Hunter, W.

(2004) Acta Crystallogr D Biol Crystallogr 60: 1780

PubMed: 15388924 Search on PubMed
DOI: https://doi.org/10.1107/S0907444904018955
Primary Citation of Related Structures:
1W0C

PubMed Abstract:
The structure of Leishmania major pteridine reductase (PTR1) in complex with NADPH and the inhibitor 2,4,6-triaminoquinazoline (TAQ) has been solved in a new crystal form by molecular replacement and refined to 2.6 A resolution. The inhibitor mimics a fragment, the pterin head group, of the archetypal antifolate drug methotrexate (MTX) and exploits similar chemical features to bind in the PTR1 active site. Despite being a much smaller molecule, TAQ displays a similar inhibition constant to that of MTX. PTR1 is a target for the development of improved therapies for infections caused by trypanosomatid parasites and this analysis provides information to assist the structure-based development of novel enzyme inhibitors.

Organizational Affiliation

Division of Biological Chemistry and Molecular Microbiology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland.

Macromolecule Content

Total Structure Weight: 268.7 kDa
Atom Count: 17,458
Modelled Residue Count: 2,130
Deposited Residue Count: 2,456
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, E A, B, C, D, E, F, G, H	307	Leishmania major	Mutation(s): 0 EC: 1.5.1.33
UniProt
Find proteins for Q01782 (Leishmania major) Explore Q01782 Go to UniProtKB: Q01782
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q01782
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
NAP Query on NAP Download Ideal Coordinates CCD File SDF format, chain T [auth F] SDF format, chain I [auth A] SDF format, chain L [auth B] SDF format, chain N [auth C] SDF format, chain P [auth D] SDF format, chain R [auth E] SDF format, chain V [auth G] SDF format, chain X [auth H] MOL2 format, chain T [auth F] MOL2 format, chain I [auth A] MOL2 format, chain L [auth B] MOL2 format, chain N [auth C] MOL2 format, chain P [auth D] MOL2 format, chain R [auth E] MOL2 format, chain V [auth G] MOL2 format, chain X [auth H] mmCIF format, chain T [auth F] mmCIF format, chain I [auth A] mmCIF format, chain L [auth B] mmCIF format, chain N [auth C] mmCIF format, chain P [auth D] mmCIF format, chain R [auth E] mmCIF format, chain V [auth G] mmCIF format, chain X [auth H]	I [auth A] L [auth B] N [auth C] P [auth D] R [auth E] I [auth A], L [auth B], N [auth C], P [auth D], R [auth E], T [auth F], V [auth G], X [auth H]	NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE C₂₁ H₂₈ N₇ O₁₇ P₃ XJLXINKUBYWONI-NNYOXOHSSA-N		Interactions Focus chain I [auth A] Focus chain L [auth B] Focus chain N [auth C] Focus chain P [auth D] Focus chain R [auth E] Focus chain T [auth F] Focus chain V [auth G] Focus chain X [auth H] Interactions & Density Focus chain I [auth A] Focus chain L [auth B] Focus chain N [auth C] Focus chain P [auth D] Focus chain R [auth E] Focus chain T [auth F] Focus chain V [auth G] Focus chain X [auth H]
TAQ Query on TAQ Download Ideal Coordinates CCD File SDF format, chain J [auth A] SDF format, chain K [auth A] SDF format, chain M [auth B] SDF format, chain O [auth C] SDF format, chain Q [auth D] SDF format, chain S [auth E] SDF format, chain U [auth F] SDF format, chain W [auth G] SDF format, chain Y [auth H] MOL2 format, chain J [auth A] MOL2 format, chain K [auth A] MOL2 format, chain M [auth B] MOL2 format, chain O [auth C] MOL2 format, chain Q [auth D] MOL2 format, chain S [auth E] MOL2 format, chain U [auth F] MOL2 format, chain W [auth G] MOL2 format, chain Y [auth H] mmCIF format, chain J [auth A] mmCIF format, chain K [auth A] mmCIF format, chain M [auth B] mmCIF format, chain O [auth C] mmCIF format, chain Q [auth D] mmCIF format, chain S [auth E] mmCIF format, chain U [auth F] mmCIF format, chain W [auth G] mmCIF format, chain Y [auth H]	J [auth A] K [auth A] M [auth B] O [auth C] Q [auth D] J [auth A], K [auth A], M [auth B], O [auth C], Q [auth D], S [auth E], U [auth F], W [auth G], Y [auth H]	2,4,6-TRIAMINOQUINAZOLINE C₈ H₉ N₅ LJBWEZVYRBKOCI-UHFFFAOYSA-N		Interactions Focus chain J [auth A] Focus chain K [auth A] Focus chain M [auth B] Focus chain O [auth C] Focus chain Q [auth D] Focus chain S [auth E] Focus chain U [auth F] Focus chain W [auth G] Focus chain Y [auth H] Interactions & Density Focus chain J [auth A] Focus chain K [auth A] Focus chain M [auth B] Focus chain O [auth C] Focus chain Q [auth D] Focus chain S [auth E] Focus chain U [auth F] Focus chain W [auth G] Focus chain Y [auth H]

Binding Affinity Annotations
ID	Source	Binding Affinity
TAQ	BindingDB: 1W0C	Kd: 5.88e+4 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.60 ?
R-Value Free: 0.337
R-Value Work: 0.267
Space Group: P 1 2₁ 1

Unit Cell:

Length ( ? )	Angle ( ? )
a = 95.851	α = 90
b = 102.945	β = 108.32
c = 146.707	γ = 90

Software Package:

Software Name	Purpose
REFMAC	refinement
DENZO	data reduction
SCALEPACK	data scaling
AMoRE	phasing

Structure Validation

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Entry History

Deposition Data

Released Date: 2004-09-30

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2004-09-30
Type: Initial release
Version 1.1: 2011-05-08
Changes: Version format compliance
Version 1.2: 2011-07-13
Changes: Version format compliance
Version 1.3: 2023-12-13
Changes: Data collection, Database references, Derived calculations, Other, Refinement description

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Help and Resources

1W0C

Inhibition of Leishmania major pteridine reductase (PTR1) by 2,4,6-triaminoquinazoline; structure of the NADP ternary complex.

Inhibition of Leishmania Major Pteridine Reductase by 2,4,6-Triaminoquinazoline: Structure of the Nadph Ternary Complex

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)