BIOSC 1540 - Project

Model 01

Oligo-State: Monomer

GMQE: 0.96

QMEANDisCo Global:: 0.91 ± 0.07

Ligands

1 x MMV, 1 x NAP

1 x 3-(2-{3-[(2,4-diamino-6-ethylpyrimidin-5-yl)oxy]propoxy}phenyl)propanoic acid

MMV.2:

13 residues within 4Å:

9 PLIP interactions:

1 x NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE

NAP.1:

27 residues within 4Å:

20 PLIP interactions:

QMEANDisCo Local

QMEAN Z-Scores

Template

6e4e.1.A Dihydrofolate reductase
Crystal structure of dihydrofolate reductase from Staphylococcus aureus MW2 bound to NADP and p218

Seq Identity: 100.00%
Coverage

Ligand	Added to Model	Description
MMV	✓	3-(2-{3-[(2,4-diamino-6-ethylpyrimidin-5-yl)oxy]propoxy}phenyl)propanoic acid
NAP	✓	NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE

Model-Template Alignment

Model 05

Oligo-State: Monomer

GMQE: 0.95

QMEANDisCo Global:: 0.91 ± 0.07

Ligands

1 x NDP, 1 x XCF

1 x NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE

NDP.1:

25 residues within 4Å:

20 PLIP interactions:

1 x 5-[[(2R)-2-cyclopropyl-7,8-dimethoxy-2H-chromen-5-yl]methyl]pyrimidine-2,4-diamine

XCF.2:

11 residues within 4Å:

10 PLIP interactions:

QMEANDisCo Local

QMEAN Z-Scores

Template

3fyw.1.A Dihydrofolate reductase
Staph. aureus DHFR complexed with NADPH and AR-101

Seq Identity: 100.00%
Coverage

Ligand	Added to Model	Description
NDP	✓	NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
XCF	✓	5-[[(2R)-2-cyclopropyl-7,8-dimethoxy-2H-chromen-5-yl]methyl]pyrimidine-2,4-diamine

Model-Template Alignment

Model 03

Oligo-State: Monomer

GMQE: 0.95

QMEANDisCo Global:: 0.91 ± 0.07

Ligands

1 x NAP, 1 x OWS

1 x NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE

NAP.1:

26 residues within 4Å:

24 PLIP interactions:

1 x (2E)-3-{5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl}-1-[(1S)-1-(4-methylphenyl)phthalazin-2(1H)-yl]prop-2-en-1-one

OWS.2:

18 residues within 4Å:

17 PLIP interactions:

QMEANDisCo Local

QMEAN Z-Scores

Template

6pr6.1.A Dihydrofolate reductase
S. aureus dihydrofolate reductase co-crystallized with para-tolyl-dihydropthalazine inhibitor and NADP(H)

Seq Identity: 100.00%
Coverage

Ligand	Added to Model	Description
NAP	✓	NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
OWS	✓	(2E)-3-{5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl}-1-[(1S)-1-(4-methylphenyl)phthalazin-2(1H)-yl]prop-2-en-1-one
GOL	✕ - Not biologically relevant.	GLYCEROL
GOL	✕ - Not biologically relevant.	GLYCEROL

Model-Template Alignment

Model 06

Oligo-State: Monomer

GMQE: 0.95

QMEANDisCo Global:: 0.91 ± 0.07

Ligands

1 x NAP, 1 x OWJ

1 x NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE

NAP.2:

26 residues within 4Å:

24 PLIP interactions:

1 x (2E)-3-{5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl}-1-[(1S)-1-(3,5-dimethylphenyl)phthalazin-2(1H)-yl]prop-2-en-1-one

OWJ.1:

16 residues within 4Å:

14 PLIP interactions:

QMEANDisCo Local

QMEAN Z-Scores

Template

6pr8.1.A Dihydrofolate reductase
S. aureus dihydrofoate reductase co-crystallized with 3,5-dimethylphenyl-dihydropthalazine inhibitor and NADP(H)

Seq Identity: 100.00%
Coverage

Ligand	Added to Model	Description
NAP	✓	NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
OWJ	✓	(2E)-3-{5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl}-1-[(1S)-1-(3,5-dimethylphenyl)phthalazin-2(1H)-yl]prop-2-en-1-one
GOL	✕ - Not biologically relevant.	GLYCEROL
GOL	✕ - Not biologically relevant.	GLYCEROL

Model-Template Alignment

Model 04

Oligo-State: Monomer

GMQE: 0.95

QMEANDisCo Global:: 0.91 ± 0.07

Ligands

1 x NAP, 1 x Q11

1 x NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE

NAP.1:

26 residues within 4Å:

23 PLIP interactions:

1 x 7-(2-methoxyphenyl)quinazoline-2,4-diamine

Q11.2:

10 residues within 4Å:

8 PLIP interactions:

QMEANDisCo Local

QMEAN Z-Scores

Template

3sqy.1.A Dihydrofolate reductase
S. aureus Dihydrofolate Reductase complexed with novel 7-aryl-2,4-diaminoquinazolines

Seq Identity: 100.00%
Coverage

Ligand	Added to Model	Description
NAP	✓	NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
Q11	✓	7-(2-methoxyphenyl)quinazoline-2,4-diamine

Model-Template Alignment

Model 07

Oligo-State: Monomer

GMQE: 0.95

QMEANDisCo Global:: 0.91 ± 0.07

Ligands

1 x NAP, 1 x Q12

1 x NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE

NAP.1:

26 residues within 4Å:

23 PLIP interactions:

1 x 7-(3,4-dimethoxyphenyl)-6-methylquinazoline-2,4-diamine

Q12.2:

12 residues within 4Å:

8 PLIP interactions:

QMEANDisCo Local

QMEAN Z-Scores

Template

3sr5.1.A Dihydrofolate reductase
S. aureus Dihydrofolate Reductase complexed with novel 7-aryl-2,4-diaminoquinazolines

Seq Identity: 100.00%
Coverage

Ligand	Added to Model	Description
NAP	✓	NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
Q12	✓	7-(3,4-dimethoxyphenyl)-6-methylquinazoline-2,4-diamine

Model-Template Alignment

Model 08

Oligo-State: Monomer

GMQE: 0.95

QMEANDisCo Global:: 0.91 ± 0.07

Ligands

1 x NDP, 1 x TOP

1 x NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE

NDP.2:

26 residues within 4Å:

21 PLIP interactions:

1 x TRIMETHOPRIM

TOP.1:

11 residues within 4Å:

7 PLIP interactions:

QMEANDisCo Local

QMEAN Z-Scores

Template

2w9g.1.A DIHYDROFOLATE REDUCTASE
Wild-type Staphylococcus aureus DHFR in complex with NADPH and trimethoprim

Seq Identity: 100.00%
Coverage

Model-Template Alignment

Model 09

Oligo-State: Monomer

GMQE: 0.94

QMEANDisCo Global:: 0.90 ± 0.07

Ligands

1 x TOP

QMEANDisCo Local

QMEAN Z-Scores

Template

2w9h.1.A DIHYDROFOLATE REDUCTASE
Wild-type Staphylococcus aureus DHFR in complex with trimethoprim

Seq Identity: 100.00%
Coverage

Model-Template Alignment

Model 02

Oligo-State: Monomer

GMQE: 0.64

QMEANDisCo Global:: 0.72 ± 0.07

Ligands

QMEANDisCo Local

QMEAN Z-Scores

Template

2w3m.1.A DIHYDROFOLATE REDUCTASE
HUMAN DIHYDROFOLATE REDUCTASE COMPLEXED WITH NADPH AND FOLATE

Seq Identity: 30.07%
Coverage

Model-Template Alignment

Biounit Oligo State	Monomer
QSQE	0.00
Method	X-ray, 1.90 Å
Seq Similarity	0.62
Coverage	1.00
Range	1-159

Biounit Oligo State	Monomer
QSQE	0.00
Method	X-ray, 2.10 Å
Seq Similarity	0.62
Coverage	0.99
Range	2-159

Biounit Oligo State	Monomer
QSQE	0.00
Method	X-ray, 2.01 Å
Seq Similarity	0.62
Coverage	1.00
Range	2-159

Biounit Oligo State	Monomer
QSQE	0.00
Method	X-ray, 2.01 Å
Seq Similarity	0.62
Coverage	0.99
Range	2-159

Biounit Oligo State	Monomer
QSQE	0.00
Method	X-ray, 1.50 Å
Seq Similarity	0.62
Coverage	1.00
Range	2-158

Ligand	Added to Model	Description
NDP	✓	NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
TOP	✓	TRIMETHOPRIM

Ligand	Added to Model	Description
TOP	✓	TRIMETHOPRIM
EDO	✕ - Not biologically relevant.	1,2-ETHANEDIOL

Ligand	Added to Model	Description
FOL	✕ - Binding site not conserved.	FOLIC ACID
NDP	✕ - Binding site not conserved.	NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE

BIOSC 1540 - Project

Created: Nov. 15, 2024, 9:23 p.m. at 21:23

Background

Resolution