8CQ8

Mycobacterium tuberculosis dihydrofolate reductase in complex with methyl 4-(2,6-diamino-5-(cyclopropylethynyl)pyrimidin-4-yl)benzoate

PDB DOI: https://doi.org/10.2210/pdb8CQ8/pdb

Classification: BIOSYNTHETIC PROTEIN
Organism(s): Mycobacterium tuberculosis
Expression System: Escherichia coli BL21(DE3)
Mutation(s): No

Deposited: 2023-03-04 Released: 2024-03-13
Deposition Author(s): Kirkman, T.J., Dias, M.V.B., Coyne, A.G.
Funding Organization(s): UK Research and Innovation (UKRI)

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.80 Å
R-Value Free: 0.240
R-Value Work: 0.209
R-Value Observed: 0.220

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.0 of the entry. See complete history.

Literature

Expansion of a series of pyrimidine derivatives utilising fragment-based merging leads to increased affinity to Mycobacterium tuberculosis dihydrofolate reductase (unpublished currently)

Kirkman, T.J., Dias, M.V.B., Coyne, A.G.

To be published.

Macromolecule Content

Total Structure Weight: 38.98 kDa
Atom Count: 2,813
Modelled Residue Count: 318
Deposited Residue Count: 322
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Dihydrofolate reductase	A, B	161	Mycobacterium tuberculosis	Mutation(s): 0 Gene Names: folA EC: 1.5.1.3
UniProt
Find proteins for P9WNX1 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)) Explore P9WNX1 Go to UniProtKB: P9WNX1
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P9WNX1
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 5 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
NDP (Subject of Investigation/LOI) Query on NDP Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain L [auth B] MOL2 format, chain E [auth A] MOL2 format, chain L [auth B] mmCIF format, chain E [auth A] mmCIF format, chain L [auth B]	E [auth A], L [auth B]	NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE C₂₁ H₃₀ N₇ O₁₇ P₃ ACFIXJIJDZMPPO-NNYOXOHSSA-N		Interactions Focus chain E [auth A] Focus chain L [auth B] Interactions & Density Focus chain E [auth A] Focus chain L [auth B]
VFF (Subject of Investigation/LOI) Query on VFF Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain I [auth B] MOL2 format, chain C [auth A] MOL2 format, chain I [auth B] mmCIF format, chain C [auth A] mmCIF format, chain I [auth B]	C [auth A], I [auth B]	methyl 4-[2,6-bis(azanyl)-5-(2-cyclopropylethynyl)pyrimidin-4-yl]benzoate C₁₇ H₁₆ N₄ O₂ VQXXOXYFIZOZAI-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Focus chain I [auth B] Interactions & Density Focus chain C [auth A] Focus chain I [auth B]
MES Query on MES Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain J [auth B] SDF format, chain K [auth B] MOL2 format, chain D [auth A] MOL2 format, chain J [auth B] MOL2 format, chain K [auth B] mmCIF format, chain D [auth A] mmCIF format, chain J [auth B] mmCIF format, chain K [auth B]	D [auth A], J [auth B], K [auth B]	2-(N-MORPHOLINO)-ETHANESULFONIC ACID C₆ H₁₃ N O₄ S SXGZJKUKBWWHRA-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Focus chain J [auth B] Focus chain K [auth B] Interactions & Density Focus chain D [auth A] Focus chain J [auth B] Focus chain K [auth B]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain H [auth A] SDF format, chain N [auth B] SDF format, chain O [auth B] MOL2 format, chain G [auth A] MOL2 format, chain H [auth A] MOL2 format, chain N [auth B] MOL2 format, chain O [auth B] mmCIF format, chain G [auth A] mmCIF format, chain H [auth A] mmCIF format, chain N [auth B] mmCIF format, chain O [auth B]	G [auth A], H [auth A], N [auth B], O [auth B]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain G [auth A] Focus chain H [auth A] Focus chain N [auth B] Focus chain O [auth B] Interactions & Density Focus chain G [auth A] Focus chain H [auth A] Focus chain N [auth B] Focus chain O [auth B]
CO Query on CO Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain M [auth B] MOL2 format, chain F [auth A] MOL2 format, chain M [auth B] mmCIF format, chain F [auth A] mmCIF format, chain M [auth B]	F [auth A], M [auth B]	COBALT (II) ION Co XLJKHNWPARRRJB-UHFFFAOYSA-N		Interactions Focus chain F [auth A] Focus chain M [auth B] Interactions & Density Focus chain F [auth A] Focus chain M [auth B]