PDB-2bfa: Leishmania major pteridine reductase 1 in complex with NADP and CB3717

ID or keywords:

Entry

Database: PDB / ID: 2bfa

Title

Leishmania major pteridine reductase 1 in complex with NADP and CB3717

Components

PTERIDINE REDUCTASE 1

Keywords

OXIDOREDUCTASE /

PTERIDINE REDUCTASE / TRYPANOSOMATIDS /

DRUG RESISTANCE / PTERIN SALVAGE /

SHORT-CHAIN DEHYDROGENASE/REDUCTASE / METHOTREXATE RESISTANCE /

NADP

Function / homology

Function and homology information

pteridine reductase /

6,7-dihydropteridine reductase activity /

pteridine reductase activity / tetrahydrobiopterin biosynthetic process / response to methotrexate /

oxidoreductase activity /

cytosol
Similarity search - Function

Biological species

LEISHMANIA MAJOR (eukaryote)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 2.7 Å

Authors

Schuettelkopf, A.W. / Hunter, W.N.

Citation

Journal: J.Mol.Biol. / Year: 2005
Title: Structures of Leishmania Major Pteridine Reductase Complexes Reveal the Active Site Features Important for Ligand Binding and to Guide Inhibitor Design
Authors: Schuettelkopf, A.W. / Hardy, L.W. / Beverley, S.M. / Hunter, W.N.

History

Deposition	Dec 6, 2004	Deposition site: PDBE / Processing site: PDBE
Revision 1.0	Aug 31, 2005	Provider: repository / Type: Initial release
Revision 1.1	May 8, 2011	Group: Version format compliance
Revision 1.2	Jul 13, 2011	Group: Version format compliance
Revision 1.3	Mar 6, 2019	Group: Data collection / Experimental preparation / Other Category: exptl_crystal_grow / pdbx_database_proc / pdbx_database_status Item: _exptl_crystal_grow.temp / _pdbx_database_status.recvd_author_approval
Revision 1.4	Dec 13, 2023	Group: Data collection / Database references ...Data collection / Database references / Other / Refinement description Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / pdbx_initial_refinement_model / struct_ncs_dom_lim Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf / _struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id / _struct_ncs_dom_lim.beg_label_comp_id / _struct_ncs_dom_lim.beg_label_seq_id / _struct_ncs_dom_lim.end_auth_comp_id / _struct_ncs_dom_lim.end_label_asym_id / _struct_ncs_dom_lim.end_label_comp_id / _struct_ncs_dom_lim.end_label_seq_id

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	2bfa.cif.gz	215 KB	Display	PDBx/mmCIF format
PDB format	pdb2bfa.ent.gz	173.1 KB	Display	PDB format
PDBx/mmJSON format	2bfa.json.gz		Tree view	PDBx/mmJSON format
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Validation report

Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/bf/2bfa ftp://data.pdbj.org/pub/pdb/validation_reports/bf/2bfa	HTTPS FTP

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Related structure data

Related structure data	2bf7C 2bfmC 2bfoC 2bfpC 1e92S 1e7w 1w0c S: Starting model for refinement C: citing same article (ref.)
Similar structure data	1e92-d 5l42-d 1e7w-1 3h4v-2 1w0c-2 2bfm-d 2bfp-d 2bf7-d 2qhx-d 2bfo-d Search similar-shape structures by Omokage search (details) Similarity search - Function & homologyF&H Search Similarity search - FunctionF&H Search Similarity search - HomologyF&H Search

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Links

PDB pages	PDBj / wwPDB / NCBI
Related items in Molecule of the Month	#90 - Jun 2007 Fatty Acid Synthase similarity (3) #77 - May 2006 Glucose Oxidase similarity (3) #188 - Aug 2015 Tetrahydrobiopterin Biosynthesis similarity (2) #216 - Dec 2017 Biodegradable Plastic similarity (2) #34 - Oct 2002 Dihydrofolate Reductase similarity (1) #57 - Sep 2004 Catalase similarity (1)

Deposited unit

A: PTERIDINE REDUCTASE 1

B: PTERIDINE REDUCTASE 1

C: PTERIDINE REDUCTASE 1

D: PTERIDINE REDUCTASE 1

hetero molecules

127 kDa, 4 polymers
Search similar-shape structures of this assembly by Omokage search (details)

1

Idetical with deposited unit
defined by author&software

Unit cell

Length a, b, c (Å)	94.538, 103.834, 137.045
Angle α, β, γ (deg.)	90.00, 90.00, 90.00
Int Tables number	19
Space group name H-M	P2₁2₁2₁

Noncrystallographic symmetry (NCS)

NCS domain:

ID	Ens-ID	Details
1	1	A
2	1	B
3	1	C
4	1	D
1	2	A
2	2	B
3	2	C
4	2	D

NCS domain segments:

Refine code: 1

Dom-ID	Component-ID	Ens-ID	Beg auth comp-ID	Beg label comp-ID	End auth comp-ID	End label comp-ID	Auth asym-ID	Label asym-ID	Auth seq-ID	Label seq-ID
1	1	1	PRO	PRO	ALA	ALA	A	A	7 - 15	7 - 15
2	1	1	PRO	PRO	ALA	ALA	B	B	7 - 15	7 - 15
3	1	1	PRO	PRO	ALA	ALA	C	C	7 - 15	7 - 15
4	1	1	PRO	PRO	ALA	ALA	D	D	7 - 15	7 - 15
1	2	1	ARG	ARG	ARG	ARG	A	A	17	17
2	2	1	ARG	ARG	ARG	ARG	B	B	17	17
3	2	1	ARG	ARG	ARG	ARG	C	C	17	17
4	2	1	ARG	ARG	ARG	ARG	D	D	17	17
1	3	1	GLY	GLY	GLY	GLY	A	A	19	19
2	3	1	GLY	GLY	GLY	GLY	B	B	19	19
3	3	1	GLY	GLY	GLY	GLY	C	C	19	19
4	3	1	GLY	GLY	GLY	GLY	D	D	19	19
1	4	1	SER	SER	LEU	LEU	A	A	21 - 35	21 - 35
2	4	1	SER	SER	LEU	LEU	B	B	21 - 35	21 - 35
3	4	1	SER	SER	LEU	LEU	C	C	21 - 35	21 - 35
4	4	1	SER	SER	LEU	LEU	D	D	21 - 35	21 - 35
1	5	1	TYR	TYR	HIS	HIS	A	A	37 - 38	37 - 38
2	5	1	TYR	TYR	HIS	HIS	B	B	37 - 38	37 - 38
3	5	1	TYR	TYR	HIS	HIS	C	C	37 - 38	37 - 38
4	5	1	TYR	TYR	HIS	HIS	D	D	37 - 38	37 - 38
1	6	1	SER	SER	ALA	ALA	A	A	40 - 42	40 - 42
2	6	1	SER	SER	ALA	ALA	B	B	40 - 42	40 - 42
3	6	1	SER	SER	ALA	ALA	C	C	40 - 42	40 - 42
4	6	1	SER	SER	ALA	ALA	D	D	40 - 42	40 - 42
1	7	1	ALA	ALA	ALA	ALA	A	A	44 - 53	44 - 53
2	7	1	ALA	ALA	ALA	ALA	B	B	44 - 53	44 - 53
3	7	1	ALA	ALA	ALA	ALA	C	C	44 - 53	44 - 53
4	7	1	ALA	ALA	ALA	ALA	D	D	44 - 53	44 - 53
1	8	1	ARG	ARG	ILE	ILE	A	A	55 - 60	55 - 60
2	8	1	ARG	ARG	ILE	ILE	B	B	55 - 60	55 - 60
3	8	1	ARG	ARG	ILE	ILE	C	C	55 - 60	55 - 60
4	8	1	ARG	ARG	ILE	ILE	D	D	55 - 60	55 - 60
1	9	1	GLN	GLN	VAL	VAL	A	A	63 - 69	63 - 69
2	9	1	GLN	GLN	VAL	VAL	B	B	63 - 69	63 - 69
3	9	1	GLN	GLN	VAL	VAL	C	C	63 - 69	63 - 69
4	9	1	GLN	GLN	VAL	VAL	D	D	63 - 69	63 - 69
1	10	1	PRO	PRO	PRO	PRO	A	A	82 - 117	82 - 117
2	10	1	PRO	PRO	PRO	PRO	B	B	82 - 117	82 - 117
3	10	1	PRO	PRO	PRO	PRO	C	C	82 - 117	82 - 117
4	10	1	PRO	PRO	PRO	PRO	D	D	82 - 117	82 - 117
1	11	1	THR	THR	ALA	ALA	A	A	138 - 159	138 - 159
2	11	1	THR	THR	ALA	ALA	B	B	138 - 159	138 - 159
3	11	1	THR	THR	ALA	ALA	C	C	138 - 159	138 - 159
4	11	1	THR	THR	ALA	ALA	D	D	138 - 159	138 - 159
1	12	1	VAL	VAL	ALA	ALA	A	A	162 - 167	162 - 167
2	12	1	VAL	VAL	ALA	ALA	B	B	162 - 167	162 - 167
3	12	1	VAL	VAL	ALA	ALA	C	C	162 - 167	162 - 167
4	12	1	VAL	VAL	ALA	ALA	D	D	162 - 167	162 - 167
1	13	1	ARG	ARG	SER	SER	A	A	170 - 227	170 - 227
2	13	1	ARG	ARG	SER	SER	B	B	170 - 227	170 - 227
3	13	1	ARG	ARG	SER	SER	C	C	170 - 227	170 - 227
4	13	1	ARG	ARG	SER	SER	D	D	170 - 227	170 - 227
1	14	1	TYR	TYR	SER	SER	A	A	248 - 267	248 - 267
2	14	1	TYR	TYR	SER	SER	B	B	248 - 267	248 - 267
3	14	1	TYR	TYR	SER	SER	C	C	248 - 267	248 - 267
4	14	1	TYR	TYR	SER	SER	D	D	248 - 267	248 - 267
1	15	1	ALA	ALA	ALA	ALA	A	A	269	269
2	15	1	ALA	ALA	ALA	ALA	B	B	269	269
3	15	1	ALA	ALA	ALA	ALA	C	C	269	269
4	15	1	ALA	ALA	ALA	ALA	D	D	269	269
1	16	1	TYR	TYR	VAL	VAL	A	A	271 - 277	271 - 277
2	16	1	TYR	TYR	VAL	VAL	B	B	271 - 277	271 - 277
3	16	1	TYR	TYR	VAL	VAL	C	C	271 - 277	271 - 277
4	16	1	TYR	TYR	VAL	VAL	D	D	271 - 277	271 - 277
1	17	1	VAL	VAL	ALA	ALA	A	A	279 - 288	279 - 288
2	17	1	VAL	VAL	ALA	ALA	B	B	279 - 288	279 - 288
3	17	1	VAL	VAL	ALA	ALA	C	C	279 - 288	279 - 288
4	17	1	VAL	VAL	ALA	ALA	D	D	279 - 288	279 - 288
1	1	2	NDP	NDP	NDP	NDP	A	E	1289
2	1	2	NDP	NDP	NDP	NDP	B	J	1289
3	1	2	NDP	NDP	NDP	NDP	C	M	1289
4	1	2	NDP	NDP	NDP	NDP	D	O	1289

NCS ensembles :

ID
1
2

NCS oper:

ID	Code	Matrix	Vector
1	given	(-0.999978, 0.004116, 0.00511), (0.004331, 0.999081, 0.042642), (-0.00493, 0.042664, -0.999077)	22.749, -2.9804, 136.7392
2	given	(-0.799087, -0.012076, 0.601094), (-0.01298, -0.999219, -0.037329), (0.601075, -0.037631, 0.798306)	-20.0824, 94.7936, 8.6798
3	given	(0.796163, 0.007856, -0.605031), (0.010659, -0.999943, 0.001043), (-0.604988, -0.007279, -0.796201)	44.097, 91.86, 131.9711

#1: Protein	PTERIDINE REDUCTASE 1 / / H REGION METHOTREXATE RESISTANCE PROTEIN Mass: 30440.580 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) LEISHMANIA MAJOR (eukaryote) / Plasmid: PET 15B / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: Q01782, pteridine reductase
#2: Chemical	ChemComp-NDP / NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE / Nicotinamide adenine dinucleotide phosphate Mass: 745.421 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C₂₁H₃₀N₇O₁₇P₃
#3: Chemical	ChemComp-CB3 / 10-PROPARGYL-5,8-DIDEAZAFOLIC ACID Mass: 477.469 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C₂₄H₂₃N₅O₆
#4: Chemical	ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL / Ethylene glycol Mass: 62.068 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C₂H₆O₂
#5: Water	ChemComp-HOH / water / Water Mass: 18.015 Da / Num. of mol.: 211 / Source method: isolated from a natural source / Formula: H₂O
Compound details	FUNCTION: EXHIBITS A NADPH-DEPENDENT BIOPTERIN REDUCTASE ACTIVITY.

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Experiment

Experiment	Method: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

Crystal	Density Matthews: 2.74 Å³/Da / Density % sol: 55 %
Crystal grow	Temperature: 293 K / pH: 5.5 Details: 15 MG/ML PROTEIN, 0.1M NAAC/HAC BUFFER PH 5.5, 10% MPEG 5000, 0.065M CAAC2, 293K

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Data collection

Diffraction	Mean temperature: 100 K
Diffraction source	Source: SYNCHROTRON / Site: ESRF / Beamline: BM14 / Wavelength: 1.033
Detector	Type: ADSC CCD / Detector: CCD
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 1.033 Å / Relative weight: 1
Reflection	Resolution: 2.7→30 Å / Num. obs: 35456 / % possible obs: 92.7 % / Redundancy: 3.9 % / B_iso Wilson estimate: 37.4 Å² / R_merge(I) obs: 0.14 / Net I/σ(I): 9.8
Reflection shell	Resolution: 2.7→2.8 Å / R_merge(I) obs: 0.41 / Mean I/σ(I) obs: 2.9 / % possible all: 85

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Processing

Software

Name	Version	Classification
REFMAC	5.1.24	refinement
DENZO		data reduction
SCALEPACK		data scaling
AMoRE		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1E92

1e92

Resolution: 2.7→24.5 Å / Cor.coef. F_o:F_c: 0.915 / Cor.coef. F_o:F_c free: 0.891 / SU ML: 0.217 / Cross valid method: THROUGHOUT / ESU R: 4.192 / ESU R Free: 0.324 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS.

	R_factor	Num. reflection	% reflection	Selection details
R_free	0.236	1764	5 %	RANDOM
R_work	0.203	-	-	-
obs	0.205	33423	100 %	-

Solvent computation

Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: BABINET MODEL WITH MASK

Displacement parameters

B_iso mean: 28.92 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	-0.46 Å²	0 Å²	0 Å²
2-	-	0.86 Å²	0 Å²
3-	-	-	-0.4 Å²

Refinement step

Cycle: LAST / Resolution: 2.7→24.5 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	7752	0	356	211	8319

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.007	0.021	8271
X-RAY DIFFRACTION	r_bond_other_d
X-RAY DIFFRACTION	r_angle_refined_deg	0.987	2.004	11287
X-RAY DIFFRACTION	r_angle_other_deg
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	2.98	5	1025
X-RAY DIFFRACTION	r_dihedral_angle_2_deg
X-RAY DIFFRACTION	r_dihedral_angle_3_deg
X-RAY DIFFRACTION	r_dihedral_angle_4_deg
X-RAY DIFFRACTION	r_chiral_restr	0.078	0.2	1314
X-RAY DIFFRACTION	r_gen_planes_refined	0.007	0.02	6150
X-RAY DIFFRACTION	r_gen_planes_other
X-RAY DIFFRACTION	r_nbd_refined	0.227	0.2	4255
X-RAY DIFFRACTION	r_nbd_other
X-RAY DIFFRACTION	r_nbtor_refined
X-RAY DIFFRACTION	r_nbtor_other
X-RAY DIFFRACTION	r_xyhbond_nbd_refined	0.147	0.2	459
X-RAY DIFFRACTION	r_xyhbond_nbd_other
X-RAY DIFFRACTION	r_metal_ion_refined
X-RAY DIFFRACTION	r_metal_ion_other
X-RAY DIFFRACTION	r_symmetry_vdw_refined	0.288	0.2	68
X-RAY DIFFRACTION	r_symmetry_vdw_other
X-RAY DIFFRACTION	r_symmetry_hbond_refined	0.227	0.2	8
X-RAY DIFFRACTION	r_symmetry_hbond_other
X-RAY DIFFRACTION	r_symmetry_metal_ion_refined
X-RAY DIFFRACTION	r_symmetry_metal_ion_other
X-RAY DIFFRACTION	r_mcbond_it	0.828	1.5	5190
X-RAY DIFFRACTION	r_mcbond_other
X-RAY DIFFRACTION	r_mcangle_it	1.697	2	8305
X-RAY DIFFRACTION	r_mcangle_other
X-RAY DIFFRACTION	r_scbond_it	2.24	3	3081
X-RAY DIFFRACTION	r_scbond_other
X-RAY DIFFRACTION	r_scangle_it	3.686	4.5	2982
X-RAY DIFFRACTION	r_scangle_other
X-RAY DIFFRACTION	r_long_range_B_refined
X-RAY DIFFRACTION	r_long_range_B_other
X-RAY DIFFRACTION	r_rigid_bond_restr
X-RAY DIFFRACTION	r_sphericity_free
X-RAY DIFFRACTION	r_sphericity_bonded

Refine LS restraints NCS

Refine-ID: X-RAY DIFFRACTION

Ens-ID	Dom-ID	Auth asym-ID	Number	Type	Rms dev position (Å)	Weight position
1	1	A	1560	tight positional	0.1	0.05
1	2	B	1560	tight positional	0.11	0.05
1	3	C	1560	tight positional	0.08	0.05
1	4	D	1560	tight positional	0.12	0.05
2	1	A	48	tight positional	0.04	0.05
2	2	B	48	tight positional	0.04	0.05
2	3	C	48	tight positional	0.04	0.05
2	4	D	48	tight positional	0.04	0.05
1	1	A	1560	tight thermal	0.13	0.5
1	2	B	1560	tight thermal	0.13	0.5
1	3	C	1560	tight thermal	0.11	0.5
1	4	D	1560	tight thermal	0.11	0.5
2	1	A	48	tight thermal	0.15	0.5
2	2	B	48	tight thermal	0.14	0.5
2	3	C	48	tight thermal	0.16	0.5
2	4	D	48	tight thermal	0.15	0.5

LS refinement shell

Resolution: 2.7→2.77 Å / Total num. of bins used: 20 /

	R_factor	Num. reflection
R_free	0.281	122
R_work	0.252	2441

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