PDB-4mjo: Human liver fructose-1,6-bisphosphatase(d-fructose-1,6-bisphospha...

Basic information

• Entry: Database: PDB / ID: 4mjo
• Title: Human liver fructose-1,6-bisphosphatase(d-fructose-1,6-bisphosphate, 1-phosphohydrolase) (e.c.3.1.3.11) complexed with the allosteric inhibitor 3
• Components: Fructose-1,6-bisphosphatase 1Fructose 1,6-bisphosphatase
• Keywords: HYDROLASE/HYDROLASE INHIBITOR / Allostery / HYDROLASE (PHOSPHORIC MONOESTER) / HYDROLASE-HYDROLASE INHIBITOR complex

Function / homology

Function:

cellular response to raffinose / sucrose biosynthetic process / cellular hypotonic salinity response / cellular response to phorbol 13-acetate 12-myristate / fructose-bisphosphatase / fructose 1,6-bisphosphate 1-phosphatase activity / negative regulation of Ras protein signal transduction / fructose 1,6-bisphosphate metabolic process / cellular response to magnesium ion / fructose 6-phosphate metabolic process / fructose metabolic process / Gluconeogenesis / monosaccharide binding / negative regulation of glycolytic process / cellular hyperosmotic salinity response / regulation of gluconeogenesis / AMP binding / dephosphorylation / cellular response to cAMP / response to nutrient levels / gluconeogenesis / negative regulation of cell growth / cellular response to insulin stimulus / cellular response to xenobiotic stimulus / RNA polymerase II-specific DNA-binding transcription factor binding / negative regulation of transcription by RNA polymerase II / extracellular exosome / identical protein binding / metal ion binding / nucleus / cytosol / cytoplasm

Domain/homology:

Fructose-1,6-bisphosphatase / Fructose-1,6-bisphosphatase, active site / Fructose-1-6-bisphosphatase class 1, C-terminal / Fructose-1-6-bisphosphatase active site. / Fructose-1,6-bisphosphatase class 1 / Fructose-1-6-bisphosphatase class I, N-terminal / Fructose-1-6-bisphosphatase, N-terminal domain / Fructose-1-6-bisphosphatase, C-terminal domain / D-Maltodextrin-Binding Protein; domain 2 - #80 / Fructose-1,6-Bisphosphatase, subunit A, domain 1 / Fructose-1,6-Bisphosphatase; Chain A, domain 1 / D-Maltodextrin-Binding Protein; domain 2 / 2-Layer Sandwich / 3-Layer(aba) Sandwich / Alpha Beta

Component:

Chem-2C1 / Fructose-1,6-bisphosphatase 1

• Biological species: Homo sapiens (human)
• Method: X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.4 Å
• Authors: Ruf, A. / Joseph, C. / Tetaz, T. / Benz, J.
• Citation: Journal: Acs Chem.Biol. / Year: 2014; Title: Determination of protein-ligand binding constants of a cooperatively regulated tetrameric enzyme using electrospray mass spectrometry.; Authors: Cubrilovic, D. / Haap, W. / Barylyuk, K. / Ruf, A. / Badertscher, M. / Gubler, M. / Tetaz, T. / Joseph, C. / Benz, J. / Zenobi, R.

History

Deposition	Sep 4, 2013	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Nov 6, 2013	Provider: repository / Type: Initial release
Revision 1.1	Jan 29, 2014	Group: Database references
Revision 1.2	Apr 25, 2018	Group: Advisory / Data collection / Source and taxonomy / Category: database_PDB_caveat / entity_src_nat / Item: _database_PDB_caveat.text
Revision 1.3	Sep 20, 2023	Group: Data collection / Database references / Derived calculations / Refinement description Category: chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_ncs_dom_lim / struct_site Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _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 / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

Assembly

Deposited unit

A: Fructose-1,6-bisphosphatase 1

B: Fructose-1,6-bisphosphatase 1

C: Fructose-1,6-bisphosphatase 1

D: Fructose-1,6-bisphosphatase 1

E: Fructose-1,6-bisphosphatase 1

F: Fructose-1,6-bisphosphatase 1

G: Fructose-1,6-bisphosphatase 1

H: Fructose-1,6-bisphosphatase 1

hetero molecules

Summary:

• 299 kDa, 8 polymers

Component details:

	Theoretical mass	Number of molelcules
Total (without water)	299,151	16
Polymers	295,099	8
Non-polymers	4,051	8
Water	11,908	661

1

A: Fructose-1,6-bisphosphatase 1

B: Fructose-1,6-bisphosphatase 1

C: Fructose-1,6-bisphosphatase 1

D: Fructose-1,6-bisphosphatase 1

hetero molecules

Summary:

• defined by author&software
• 150 kDa, 4 polymers

Component details:

	Theoretical mass	Number of molelcules
Total (without water)	149,575	8
Polymers	147,550	4
Non-polymers	2,026	4
Water	72	4

Symmetry operations:

Type	Name	Symmetry operation	Number
identity operation	1_555	x,y,z	1

Calculated values:

Buried area	16110 Å2
ΔGint	-79 kcal/mol
Surface area	44390 Å2
Method	PISA

2

E: Fructose-1,6-bisphosphatase 1

F: Fructose-1,6-bisphosphatase 1

G: Fructose-1,6-bisphosphatase 1

H: Fructose-1,6-bisphosphatase 1

hetero molecules

Summary:

• defined by author&software
• 150 kDa, 4 polymers

Component details:

	Theoretical mass	Number of molelcules
Total (without water)	149,575	8
Polymers	147,550	4
Non-polymers	2,026	4
Water	72	4

Symmetry operations:

Type	Name	Symmetry operation	Number
identity operation	1_555	x,y,z	1

Calculated values:

Buried area	16120 Å2
ΔGint	-80 kcal/mol
Surface area	44210 Å2
Method	PISA

Unit cell

Length a, b, c (Å)	65.974, 286.305, 83.692
Angle α, β, γ (deg.)	90.00, 97.79, 90.00
Int Tables number	4
Space group name H-M	P1211

Noncrystallographic symmetry (NCS)

NCS domain:

ID	Ens-ID	Details
1	1	A
2	1	B
1	2	A
2	2	C
1	3	A
2	3	D
1	4	A
2	4	E
1	5	A
2	5	F
1	6	A
2	6	G
1	7	A
2	7	H
1	8	B
2	8	C
1	9	B
2	9	D
1	10	B
2	10	E
1	11	B
2	11	F
1	12	B
2	12	G
1	13	B
2	13	H
1	14	C
2	14	D
1	15	C
2	15	E
1	16	C
2	16	F
1	17	C
2	17	G
1	18	C
2	18	H
1	19	D
2	19	E
1	20	D
2	20	F
1	21	D
2	21	G
1	22	D
2	22	H
1	23	E
2	23	F
1	24	E
2	24	G
1	25	E
2	25	H
1	26	F
2	26	G
1	27	F
2	27	H
1	28	G
2	28	H

NCS domain segments:

Component-ID: 0 / Beg auth comp-ID: ASP / Beg label comp-ID: ASP / End auth comp-ID: SER / End label comp-ID: SER / Refine code: 0 / Auth seq-ID: 9 - 335 / Label seq-ID: 10 - 336

Dom-ID	Ens-ID	Auth asym-ID	Label asym-ID
1	1	A	A
2	1	B	B
1	2	A	A
2	2	C	C
1	3	A	A
2	3	D	D
1	4	A	A
2	4	E	E
1	5	A	A
2	5	F	F
1	6	A	A
2	6	G	G
1	7	A	A
2	7	H	H
1	8	B	B
2	8	C	C
1	9	B	B
2	9	D	D
1	10	B	B
2	10	E	E
1	11	B	B
2	11	F	F
1	12	B	B
2	12	G	G
1	13	B	B
2	13	H	H
1	14	C	C
2	14	D	D
1	15	C	C
2	15	E	E
1	16	C	C
2	16	F	F
1	17	C	C
2	17	G	G
1	18	C	C
2	18	H	H
1	19	D	D
2	19	E	E
1	20	D	D
2	20	F	F
1	21	D	D
2	21	G	G
1	22	D	D
2	22	H	H
1	23	E	E
2	23	F	F
1	24	E	E
2	24	G	G
1	25	E	E
2	25	H	H
1	26	F	F
2	26	G	G
1	27	F	F
2	27	H	H
1	28	G	G
2	28	H	H

NCS ensembles :

ID
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28

Components

#1: Protein

A B C D E F G H
Fructose-1,6-bisphosphatase 1 / Fructose 1,6-bisphosphatase / FBPase 1 / D-fructose-1 / 6-bisphosphate 1-phosphohydrolase 1

Details:

Mass: 36887.434 Da / Num. of mol.: 8 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Organ: LIVER / References: UniProt: P09467, fructose-bisphosphatase

#2: Chemical

A-401 B-401 C-401 D-401 E-401 F-401 G-401 H-401
ChemComp-2C1 / N-({4-bromo-6-[(methylcarbamoyl)amino]pyridin-2-yl}carbamoyl)-5-(2-methoxyethyl)-4-methylthiophene-2-sulfonamide

Details:

Mass: 506.395 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: C₁₆H₂₀BrN₅O₅S₂

#3: Water

ChemComp-HOH / water / Water

Details:

Mass: 18.015 Da / Num. of mol.: 661 / Source method: isolated from a natural source / Formula: H₂O

Experimental details

Experiment

• Experiment: Method: X-RAY DIFFRACTION

Sample preparation

• Crystal: Density Matthews: 2.66 ų/Da / Density % sol: 53.69 %
• Crystal grow: Temperature: 300 K / Method: vapor diffusion, sitting drop / pH: 7 ; Details: 0.1 M ammonium acetate and 12% polyethylenglycol 3350 in 0.1 M HEPES, pH 7, VAPOR DIFFUSION, SITTING DROP, temperature 300K

Data collection

• Diffraction source: Source: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 1 Å
• Detector: Type: MAR CCD 165 mm / Detector: CCD / Date: Mar 16, 2007
• Radiation: Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
• Radiation wavelength: Wavelength: 1 Å / Relative weight: 1
• Reflection: Resolution: 2.4→30.5 Å / Num. all: 119425 / Num. obs: 115242 / % possible obs: 96.5 %

Processing

• Software: Name: REFMAC / Version: 5.2.0019 / Classification: refinement

Refinement

Method to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 2VT5

2vt5

Resolution: 2.4→29.74 Å / Cor.coef. F_o:F_c: 0.931 / Cor.coef. F_o:F_c free: 0.905 / SU B: 10.168 / SU ML: 0.225 / Cross valid method: THROUGHOUT / ESU R: 0.436 / ESU R Free: 0.252 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS

	Rfactor	Num. reflection	% reflection	Selection details
Rfree	0.23647	5784	5 %	RANDOM
Rwork	0.20664	-	-	-
obs	0.20817	109458	96.52 %	-
all	-	115242	-	-

• Solvent computation: Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK

Displacement parameters

B_iso mean: 35.597 Ų

	Baniso -1	Baniso -2	Baniso -3
1-	-0 Å2	-0 Å2	-0.33 Å2
2-	-	0.48 Å2	0 Å2
3-	-	-	-0.37 Å2

Refinement step

Cycle: LAST / Resolution: 2.4→29.74 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	19457	0	232	661	20350

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.011	0.019	20074
X-RAY DIFFRACTION	r_bond_other_d	0.008	0.02	19609
X-RAY DIFFRACTION	r_angle_refined_deg	1.521	2.001	27116
X-RAY DIFFRACTION	r_angle_other_deg	1.53	3	45262
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	5.703	5	2525
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	39.169	24.118	782
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	16.859	15	3557
X-RAY DIFFRACTION	r_dihedral_angle_4_deg	14.991	15	110
X-RAY DIFFRACTION	r_chiral_restr	0.078	0.2	3063
X-RAY DIFFRACTION	r_gen_planes_refined	0.008	0.021	22337
X-RAY DIFFRACTION	r_gen_planes_other	0.007	0.02	4157
X-RAY DIFFRACTION	r_nbd_refined
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	0.172	0.2	1075
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	0.205	0.2	67
X-RAY DIFFRACTION	r_symmetry_vdw_other
X-RAY DIFFRACTION	r_symmetry_hbond_refined	0.195	0.2	17
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	2.304	3.351	10148
X-RAY DIFFRACTION	r_mcbond_other	2.303	3.351	10147
X-RAY DIFFRACTION	r_mcangle_it	3.6	5.02	12657
X-RAY DIFFRACTION	r_mcangle_other
X-RAY DIFFRACTION	r_scbond_it	3.041	3.78	9926
X-RAY DIFFRACTION	r_scbond_other
X-RAY DIFFRACTION	r_scangle_it
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 / Type: interatomic distance / Weight position: 0.05

Ens-ID	Dom-ID	Auth asym-ID	Number	Rms dev position (Å)
1	1	A	19216	0.09
1	2	B	19216	0.09
2	1	A	18939	0.09
2	2	C	18939	0.09
3	1	A	19216	0.08
3	2	D	19216	0.08
4	1	A	19831	0.06
4	2	E	19831	0.06
5	1	A	19195	0.09
5	2	F	19195	0.09
6	1	A	18967	0.09
6	2	G	18967	0.09
7	1	A	19058	0.09
7	2	H	19058	0.09
8	1	B	19148	0.09
8	2	C	19148	0.09
9	1	B	19055	0.1
9	2	D	19055	0.1
10	1	B	19185	0.09
10	2	E	19185	0.09
11	1	B	19636	0.08
11	2	F	19636	0.08
12	1	B	19149	0.09
12	2	G	19149	0.09
13	1	B	19064	0.1
13	2	H	19064	0.1
14	1	C	18932	0.1
14	2	D	18932	0.1
15	1	C	18915	0.09
15	2	E	18915	0.09
16	1	C	19101	0.09
16	2	F	19101	0.09
17	1	C	19650	0.06
17	2	G	19650	0.06
18	1	C	18922	0.09
18	2	H	18922	0.09
19	1	D	19186	0.08
19	2	E	19186	0.08
20	1	D	19039	0.1
20	2	F	19039	0.1
21	1	D	18943	0.1
21	2	G	18943	0.1
22	1	D	19736	0.06
22	2	H	19736	0.06
23	1	E	19142	0.09
23	2	F	19142	0.09
24	1	E	18940	0.09
24	2	G	18940	0.09
25	1	E	19021	0.09
25	2	H	19021	0.09
26	1	F	19094	0.09
26	2	G	19094	0.09
27	1	F	19023	0.1
27	2	H	19023	0.1
28	1	G	18942	0.09
28	2	H	18942	0.09

LS refinement shell

Resolution: 2.4→2.462 Å / Total num. of bins used: 20

	Rfactor	Num. reflection	% reflection
Rfree	0.372	370	-
Rwork	0.326	7161	-
obs	-	-	85.57 %