SAXSdb — 5eak

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1. Protein Identity and Related Structures Protein Identity & Related Structures

Serine/threonine-protein kinase MARK2

Homo sapiens

State in the Current Structure

Assembly	Oligomeric State	Construct	Mutations and Modifications	Ligands, Ions and Associated Components	Method and Experimental Conditions	Structure Quality
1	Protein monomer Monomer Protein × 1 PDB declaration: monomeric（1） Consistent with protein copy count	Chain A； UniProt 39–364	Fragment：CATALYTIC DOMAIN (UNP RESIDUES 39-364)	24R N-[(1S,2R)-2-aminocyclohexyl]-4-[6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide × 1	X-RAY DIFFRACTION X-ray crystallization conditions：VAPOR DIFFUSION, HANGING DROP；pH 6.5；298 K；0.1M BIS-TRIS PH 6.5, 14% PEG3350, 200MM AMM.SULFATE	Resolution 2.80 Å R-free 0.254
2	Protein monomer Monomer Protein × 1 PDB declaration: monomeric（1） Consistent with protein copy count	Chain B； UniProt 39–364	Fragment：CATALYTIC DOMAIN (UNP RESIDUES 39-364)	24R N-[(1S,2R)-2-aminocyclohexyl]-4-[6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide × 1	X-RAY DIFFRACTION X-ray crystallization conditions：VAPOR DIFFUSION, HANGING DROP；pH 6.5；298 K；0.1M BIS-TRIS PH 6.5, 14% PEG3350, 200MM AMM.SULFATE	Resolution 2.80 Å R-free 0.254

Other States of the Same Protein in the Database

Each row is a biological assembly of the same UniProt protein in another PDB entry. The “Difference from current entry” column identifies evidence-level differences; no tag means the currently parsed fields agree.

Other PDB	Difference from Current Entry 5EAK	Assembly / Oligomeric State	Construct	Mutations and Modifications	Ligands, Ions and Non-polymers	Method and Experimental Conditions	Structure Quality
3IEC Helicobacter pylori CagA Inhibits PAR1/MARK Family Kinases by Mimicking Host Substrates Deposited 2009-07-22	Different construct Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 2 PDB declaration: dimeric	Chain A 49–363（315 aa） Fragment：UNP RESIDUES 49-363	Not recorded	No recorded non-water small molecule	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；296 K；Initial crystals were grown by vapor diffusion using hanging drops formed from mixing a 2:1 volume ratio of the protein complex with an equilibration buffer consisting of 22.5-25% polyethylene glycol (PEG) molecular weight 3350 Da, 300 mM Li2SO4, and 100 mM Bis-Tris pH 5.8-6.2, at 23 C. Higher quality crystals were obtained by micro-seeding and addition of 5% PEG 400 as an additive. For cryoprotection crystals where transferred directly into a buffer with a 25% PEG 3350 Da, 5-10% PEG 400 Da, 300mM Li2SO4, 100mM Bis-Tris pH 5.8-6.2, 7.5% glycerol, and flash-cooled immediately afterward to -160 C. , VAPOR DIFFUSION, HANGING DROP, temperature 296K	Resolution 2.20 Å R-free 0.248
3IEC Helicobacter pylori CagA Inhibits PAR1/MARK Family Kinases by Mimicking Host Substrates Deposited 2009-07-22	Different construct Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 2 Protein heterocomplex Heteromer；Protein × 2 PDB declaration: dimeric	Chain B 49–363（315 aa） Fragment：UNP RESIDUES 49-363	Not recorded	No recorded non-water small molecule	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；296 K；Initial crystals were grown by vapor diffusion using hanging drops formed from mixing a 2:1 volume ratio of the protein complex with an equilibration buffer consisting of 22.5-25% polyethylene glycol (PEG) molecular weight 3350 Da, 300 mM Li2SO4, and 100 mM Bis-Tris pH 5.8-6.2, at 23 C. Higher quality crystals were obtained by micro-seeding and addition of 5% PEG 400 as an additive. For cryoprotection crystals where transferred directly into a buffer with a 25% PEG 3350 Da, 5-10% PEG 400 Da, 300mM Li2SO4, 100mM Bis-Tris pH 5.8-6.2, 7.5% glycerol, and flash-cooled immediately afterward to -160 C. , VAPOR DIFFUSION, HANGING DROP, temperature 296K	Resolution 2.20 Å R-free 0.248
3IEC Helicobacter pylori CagA Inhibits PAR1/MARK Family Kinases by Mimicking Host Substrates Deposited 2009-07-22	Different construct Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 3 Protein heterocomplex Heteromer；Protein × 2 PDB declaration: dimeric	Chain C 49–363（315 aa） Fragment：UNP RESIDUES 49-363	Not recorded	No recorded non-water small molecule	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；296 K；Initial crystals were grown by vapor diffusion using hanging drops formed from mixing a 2:1 volume ratio of the protein complex with an equilibration buffer consisting of 22.5-25% polyethylene glycol (PEG) molecular weight 3350 Da, 300 mM Li2SO4, and 100 mM Bis-Tris pH 5.8-6.2, at 23 C. Higher quality crystals were obtained by micro-seeding and addition of 5% PEG 400 as an additive. For cryoprotection crystals where transferred directly into a buffer with a 25% PEG 3350 Da, 5-10% PEG 400 Da, 300mM Li2SO4, 100mM Bis-Tris pH 5.8-6.2, 7.5% glycerol, and flash-cooled immediately afterward to -160 C. , VAPOR DIFFUSION, HANGING DROP, temperature 296K	Resolution 2.20 Å R-free 0.248
3IEC Helicobacter pylori CagA Inhibits PAR1/MARK Family Kinases by Mimicking Host Substrates Deposited 2009-07-22	Different construct Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 4 Protein heterocomplex Heteromer；Protein × 2 PDB declaration: dimeric	Chain D 49–363（315 aa） Fragment：UNP RESIDUES 49-363	Not recorded	No recorded non-water small molecule	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；296 K；Initial crystals were grown by vapor diffusion using hanging drops formed from mixing a 2:1 volume ratio of the protein complex with an equilibration buffer consisting of 22.5-25% polyethylene glycol (PEG) molecular weight 3350 Da, 300 mM Li2SO4, and 100 mM Bis-Tris pH 5.8-6.2, at 23 C. Higher quality crystals were obtained by micro-seeding and addition of 5% PEG 400 as an additive. For cryoprotection crystals where transferred directly into a buffer with a 25% PEG 3350 Da, 5-10% PEG 400 Da, 300mM Li2SO4, 100mM Bis-Tris pH 5.8-6.2, 7.5% glycerol, and flash-cooled immediately afterward to -160 C. , VAPOR DIFFUSION, HANGING DROP, temperature 296K	Resolution 2.20 Å R-free 0.248
5KZ7 Mark2 complex with 7-[(1S)-1-(4-fluorophenyl)ethyl]-5,5-dimethyl-2-(3-pyridylamino)pyrrolo[2,3-d]pyrimidin-6-one Deposited 2016-07-23	Different construct Different ligand/ion Different structure-quality metrics	Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain A 6–331（326 aa） Fragment：UNP residues 6-331	Not recorded	6Z2 7-[(1~{S})-1-(4-fluorophenyl)ethyl]-5,5-dimethyl-2-(pyridin-3-ylamino)pyrrolo[2,3-d]pyrimidin-6-one × 1	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；pH 6.5；298 K；0.1M BIS-TRIS PH 6.5, 14% PEG3350, 200MM AMM.SULFATE	Resolution 3.20 Å R-free 0.293
5KZ7 Mark2 complex with 7-[(1S)-1-(4-fluorophenyl)ethyl]-5,5-dimethyl-2-(3-pyridylamino)pyrrolo[2,3-d]pyrimidin-6-one Deposited 2016-07-23	Different construct Different ligand/ion Different structure-quality metrics	Assembly 2 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain B 6–331（326 aa） Fragment：UNP residues 6-331	Not recorded	6Z2 7-[(1~{S})-1-(4-fluorophenyl)ethyl]-5,5-dimethyl-2-(pyridin-3-ylamino)pyrrolo[2,3-d]pyrimidin-6-one × 1	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；pH 6.5；298 K；0.1M BIS-TRIS PH 6.5, 14% PEG3350, 200MM AMM.SULFATE	Resolution 3.20 Å R-free 0.293
5KZ8 Mark2 complex with 7-[(1S)-1-(4-fluorophenyl)ethyl]-5,5-dimethyl-2-(3-pyridylamino)pyrrolo[2,3-d]pyrimidin-6-one Deposited 2016-07-23	Different construct Different ligand/ion Different structure-quality metrics	Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain A 6–331（326 aa） Fragment：UNP residues 6-331	Not recorded	6Z5 5,5-dimethyl-7-[(1~{S})-4-oxidanyl-1~{H}-inden-1-yl]-2-phenylazanyl-pyrrolo[2,3-d]pyrimidin-6-one × 1	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；pH 6.5；298 K；0.1M BIS-TRIS PH 6.5, 14% PEG3350, 200MM AMM.SULFATE	Resolution 3.21 Å R-free 0.290
5KZ8 Mark2 complex with 7-[(1S)-1-(4-fluorophenyl)ethyl]-5,5-dimethyl-2-(3-pyridylamino)pyrrolo[2,3-d]pyrimidin-6-one Deposited 2016-07-23	Different construct Different ligand/ion Different structure-quality metrics	Assembly 2 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain B 6–331（326 aa） Fragment：UNP residues 6-331	Not recorded	6Z5 5,5-dimethyl-7-[(1~{S})-4-oxidanyl-1~{H}-inden-1-yl]-2-phenylazanyl-pyrrolo[2,3-d]pyrimidin-6-one × 1	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；pH 6.5；298 K；0.1M BIS-TRIS PH 6.5, 14% PEG3350, 200MM AMM.SULFATE	Resolution 3.21 Å R-free 0.290
8TXY X-ray crystal structure of JRD-SIK1/2i-3 bound to a MARK2-SIK2 chimera Deposited 2023-08-24	Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain A 47–363（317 aa）	Mutation：I59L, K66V V81I, L97I, V113I, M129T, S133K, G134N , S197G	PEG DI(HYDROXYETHYL)ETHER × 2 SJ0 N-[(5P,8R)-5-(2-cyano-5-{[(3R)-1-methylpyrrolidin-3-yl]methoxy}pyridin-4-yl)pyrazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxamide × 1 SO4 SULFATE ION × 1	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION；pH 6.8；298 K；24% PEG 400, 150 mM LiSO4, 100 mM MES ph 6.8	Resolution 2.10 Å R-free 0.267
8TXY X-ray crystal structure of JRD-SIK1/2i-3 bound to a MARK2-SIK2 chimera Deposited 2023-08-24	Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 2 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain B 47–363（317 aa）	Mutation：I59L, K66V V81I, L97I, V113I, M129T, S133K, G134N , S197G	PEG DI(HYDROXYETHYL)ETHER × 1 SJ0 N-[(5P,8R)-5-(2-cyano-5-{[(3R)-1-methylpyrrolidin-3-yl]methoxy}pyridin-4-yl)pyrazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxamide × 1	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION；pH 6.8；298 K；24% PEG 400, 150 mM LiSO4, 100 mM MES ph 6.8	Resolution 2.10 Å R-free 0.267

4 other PDB entries and 10 assemblies. Open the comparison page and filter oligomeric states

View Construct and Data Evidence

UniProt name	MARK2_HUMAN
Isoform	—
PDB entities	1
Chains and sequence ranges	Author chain A； PDBConstruct 3–328； UniProt 39–364 Author chain B； PDBConstruct 3–328； UniProt 39–364

The page prioritizes protein identity, the current assembly, associated components, oligomeric state and cross-PDB links. Chain mapping and sequence ranges are retained as data evidence. Internal IDs, import timestamps and assembly operation expressions are maintenance fields and are not shown here.

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2. Structure Basics 2. Structure Basics

Entry ID entry_id	5eak
Deposition date deposition_date	2015-10-16
Structure title title	Optimization of Microtubule Affinity Regulating Kinase (MARK) Inhibitors with Improved Physical Properties
Keywords keywords	;CATALYTIC DOMAIN, PROTEIN-SERINE-THREONINE KINASES, KINASE INHIBITOR, SERINE-THREONINE KINASES, TRANSFERASE-TRANSFERASE INHIBITOR COMPLEX ;; TRANSFERASE/TRANSFERASE INHIBITOR
Experimental Method method	X-RAY DIFFRACTION

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3. SAXS Parameters (CRYSOL theoretical calculation) 3. SAXS Parameters (CRYSOL)

Radius of gyration Rg (Guinier) rg_guinier	29.31 Å
Radius of gyration Rg (electron density) rg_electron	28.37 Å
Forward intensity I(0) i0	76041000.00
Molecular weight molecular_weight	70679.0 kDa
Excluded volume excluded_volume	89621 Å³
Envelope volume envelope_volume	114190 Å³
Hydration-shell volume shell_volume	33358 Å³
Envelope diameter envelope_diameter	92.5 Å
Shell Rg shell_rg	35.80 Å
Envelope Rg envelope_rg	28.03 Å
Shape Rg shape_rg	28.36 Å
Total Rg total_rg	29.19 Å
Total atoms total_atoms	4975
Residues n_residues	605
Spherical-harmonic order n_harmonics	20
q range q_range	— – 0.5000 Å⁻¹
Data points n_points	101
Shell type shell_type	directional
Solvent electron density solvent_density	0.3340 e/Å³
Shell contrast contrast_shell	0.0300 e/Å³
CRYSOL version crysol_version	4.1.3

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4. P(r) Distance Distribution (GNOM inversion) 4. P(r) Analysis (GNOM)

Maximum dimension Dmax dmax	90.0 Å
Rg (real space) rg_real	29.20 Å
Rg uncertainty (real space) rg_real_error	0.71 Å
I(0) (real space) i0_real	7.6040e+07
I(0) uncertainty (real space) i0_real_error	1.1530e+06
Rg (reciprocal space) rg_reciprocal	29.25 Å
I(0) (reciprocal space) i0_reciprocal	76040000.0000
Solution quality estimate total_estimate	0.9124
Solution quality rating solution_quality	EXCELLENT a EXCELLENT solution
P(r) peaks n_peaks	1
Primary peak position r_peak_primary	36.7 Å
Skewness Skewness skewness	0.138
Kurtosis Kurtosis kurtosis	-0.625
Angular range angular_range	— – 0.2700 Å⁻¹
Current regularization parameter α current_alpha	0.0000
Highest regularization parameter α highest_alpha	12690000.0000
Real-space data points n_real_points	55
GNOM version gnom_version	4.1.3
Quality Criteria quality_criteria	AN1: 0.000; Oscil: 0.970; Stabil: 1.000; Sysdev: 1.000; Positv: 1.000; Valcen: 0.999; Smooth: 0.949

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5. Crystallography and Experiment 5. Crystallography & Experiment

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6. Entities and Polymers Entities & Polymers (3)

Entity 1 Entity 1 polymer

Description description	Serine/threonine-protein kinase MARK2
Molecular weight formula_weight	37832.7 kDa
EC 编号 ec_number	2.7.11.1,2.7.11.26
Source method src_method	man
Copy count entity_count	2

Polymer Polymer

Polymer type type	polypeptide(L)
Chain IDs strand_id	A,B
Atom count atom_count	4981

KLNSATSADEQPHIGNYRLLKTIGKGNFAKVKLARHILTGKEVAVKIIDKTQLNSSSLQKLFREVRIMKVLNHPNIVKLFEVIETEKTLYLVMEYASGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKFIVHRDLKAENLLLDADMNIKIADFGFSNEFTFGNKLDTFCGSPPYAAPELFQGKKYDGPEVDVWSLGVILYTLVSGSLPFDGQNLKELRERVLRGKYRIPFYMSTDCENLLKKFLILNPSKRGTLEQIMKDRWMNVGHEDDELKPYVEPLPDYKDPRRTELMVSMGYTREEIQDSLVGQRYNEVMATYLLLGYK

来源 Source

来源生物 organism	Homo sapiens
通用名 common_name	Human
NCBI Class编号 ncbi_taxonomy_id	9606
宿主生物 host_organism	Escherichia coli BL21(DE3)

Entity 2 Entity 2 non-polymer

Description description	N-[(1S,2R)-2-aminocyclohexyl]-4-[6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide
Molecular weight formula_weight	421.5 kDa
Source method src_method	syn
Copy count entity_count	2

Entity 3 Entity 3 water

Description description	water
Molecular weight formula_weight	18.0 kDa
Source method src_method	nat
Copy count entity_count	6

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7. Fold Classification (SCOP + CATH) 4 domains

SCOP 2.08 (2 domains)

Domain ID domain_id	d5eaka_
Class class	d — Alpha and beta proteins (a+b)
Fold Fold fold	d.144 — Protein kinase-like (PK-like)
Superfamily Superfamily superfamily	d.144.1 — Protein kinase-like (PK-like)
Family Family family	d.144.1.0 — automated matches

Domain ID domain_id	d5eakb_
Class class	d — Alpha and beta proteins (a+b)
Fold Fold fold	d.144 — Protein kinase-like (PK-like)
Superfamily Superfamily superfamily	d.144.1 — Protein kinase-like (PK-like)
Family Family family	d.144.1.0 — automated matches

CATH v4.4 (2 domains)

Domain ID domain_id	5eakA01
Class class	1 — Mainly Alpha
Architecture architecture	10 — Orthogonal Bundle
Topology topology	510 — Transferase(Phosphotransferase); domain 1
Homologous superfamily homologous superfamily	10 — Transferase(Phosphotransferase) domain 1

Domain ID domain_id	5eakB01
Class class	1 — Mainly Alpha
Architecture architecture	10 — Orthogonal Bundle
Topology topology	510 — Transferase(Phosphotransferase); domain 1
Homologous superfamily homologous superfamily	10 — Transferase(Phosphotransferase) domain 1

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8. Citations (1)

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Unit-cell length a length_a	118.739 Å
Unit-cell length b length_b	118.739 Å
Unit-cell length c length_c	106.592 Å
Unit-cell angle α angle_alpha	90.00 °
Unit-cell angle β angle_beta	90.00 °
Unit-cell angle γ angle_gamma	120.00 °
Molecules per unit cell Z z_pdb	12

Space group space_group	P 61
Space-group number int_tables_number	169
Crystal system crystal_system	—

Resolution resolution	2.800 Å
Low-resolution limit resolution_low	29.680 Å
R factor r_factor	0.1980
R_work r_work	0.1950
R_free r_free	0.2540

fit	/app/data/saxs_computation/ea/5eak/5eak.fit
pddf	/app/data/pr_computation/ea/5eak/5eak.pr.out
profile	/app/data/saxs_computation/ea/5eak/5eak.dat

Optimization of Microtubule Affinity Regulating Kinase (MARK) Inhibitors with Improved Physical Properties

1. Protein Identity and Related Structures Protein Identity & Related Structures

Serine/threonine-protein kinase MARK2

State in the Current Structure

Other States of the Same Protein in the Database

SAXS scattering curve SAXS Profile

P(r) Distance Distribution P(r) Distribution

2. Structure Basics 2. Structure Basics

3. SAXS Parameters (CRYSOL theoretical calculation) 3. SAXS Parameters (CRYSOL)

4. P(r) Distance Distribution (GNOM inversion) 4. P(r) Analysis (GNOM)

5. Crystallography and Experiment 5. Crystallography & Experiment

Unit cell Unit Cell

Symmetry Symmetry

Refinement Refinement

Diffraction experiment Diffraction