2viv

Fragment-Based Discovery of Mexiletine Derivatives as Orally Bioavailable Inhibitors of Urokinase-Type Plasminogen Activator

Method: X-RAY DIFFRACTION Dmax: 58.6 Å Quality: GOOD

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

UROKINASE-TYPE PLASMINOGEN ACTIVATOR CHAIN B

HOMO SAPIENS

UniProt P00749

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 179–431 Fragment:CATALYTIC DOMAIN, RESIDUES 179-431 Mutation:YES ACT ACETATE ION × 1 VG2 4-(2-aminoethoxy)-N-(3-chloro-5-piperidin-1-ylphenyl)-3,5-dimethylbenzamide × 1 X-RAY DIFFRACTION X-ray crystallization conditions:pH 6.6;PROTEIN WAS CRYSTALLIZED FROM 22-24% PEG4000, 0.17M (NH4)2SO4, 15% GLYCEROL, 0.1M NA(CH3COO) PH=4.0; THEN SOAKED IN 0.04M COMPOUND, 28% PEG4000, 5% GLYCEROL, 0.29M BISTRIS PH=6.6, 0.001M NA(CH3COO), 0.001M (NH4)2SO4 Resolution 1.72 Å R-free 0.238

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.

147 other PDB entries and 165 assemblies. Open the comparison page and filter oligomeric states

View Construct and Data Evidence
UniProt name UROK_HUMAN
Isoform
PDB entities 1
Chains and sequence ranges Author chain A; PDBConstruct 1–253; UniProt 179–431

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.

SAXS scattering curve SAXS Profile

SAXS profile for 2viv

P(r) Distance Distribution P(r) Distribution

P(r) distribution for 2viv
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2. Structure Basics 2. Structure Basics

Entry ID entry_id2viv
Deposition date deposition_date2007-12-05
Structure title titleFragment-Based Discovery of Mexiletine Derivatives as Orally Bioavailable Inhibitors of Urokinase-Type Plasminogen Activator
Keywords keywords;PLASMINOGEN ACTIVATION, EGF-LIKE DOMAIN, BLOOD COAGULATION, INHIBITOR, POLYMORPHISM, GLYCOPROTEIN, FIBRINOLYSIS, KRINGLE, ZYMOGEN, SECRETED, PROTEASE, HYDROLASE, UROKINASE-TYPE PLASMINOGEN ACTIVATOR, PHARMACEUTICAL, SERINE PROTEASE, PHOSPHORYLATION ;; HYDROLASE
Experimental Method methodX-RAY DIFFRACTION

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

Radius of gyration Rg (Guinier) rg_guinier18.33
Radius of gyration Rg (electron density) rg_electron17.09
Forward intensity I(0) i014558100.00
Molecular weight molecular_weight28273.0 kDa
Excluded volume excluded_volume35189 ų
Envelope volume envelope_volume39169 ų
Hydration-shell volume shell_volume18656 ų
Envelope diameter envelope_diameter58.5
Shell Rg shell_rg23.88
Envelope Rg envelope_rg17.51
Shape Rg shape_rg17.07
Total Rg total_rg18.14
Total atoms total_atoms1984
Residues n_residues229
Spherical-harmonic order n_harmonics20
q range q_range— – 0.5000 −1
Data points n_points101
Shell type shell_typedirectional
Solvent electron density solvent_density0.3340 e/ų
Shell contrast contrast_shell0.0300 e/ų
CRYSOL version crysol_version4.1.3

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

Maximum dimension Dmax dmax58.6
Rg (real space) rg_real18.22
Rg uncertainty (real space) rg_real_error0.27
I(0) (real space) i0_real1.4560e+07
I(0) uncertainty (real space) i0_real_error1.6850e+05
Rg (reciprocal space) rg_reciprocal18.23
I(0) (reciprocal space) i0_reciprocal14560000.0000
Solution quality estimate total_estimate0.8876
Solution quality rating solution_quality GOOD a GOOD solution
P(r) peaks n_peaks2
Primary peak position r_peak_primary23.8
Skewness Skewness skewness0.164
Kurtosis Kurtosis kurtosis-0.349
Angular range angular_range— – 0.4350 −1
Current regularization parameter α current_alpha0.0000
Highest regularization parameter α highest_alpha4267000.0000
Real-space data points n_real_points75
GNOM version gnom_version4.1.3
Quality Criteria quality_criteria AN1: 0.000; Oscil: 0.850; Stabil: 1.000; Sysdev: 1.000; Positv: 1.000; Valcen: 0.987; Smooth: 0.998

5. Crystallography and Experiment 5. Crystallography & Experiment

6. Entities and Polymers Entities & Polymers (4)

7. Fold Classification (SCOP + CATH) 3 domains

SCOP 2.08 (1 domains)

Domain ID domain_idd2viva_
Class classb — All beta proteins
Fold Fold foldb.47 — Trypsin-like serine proteases
Superfamily Superfamily superfamilyb.47.1 — Trypsin-like serine proteases
Family Family familyb.47.1.2 — Eukaryotic proteases

CATH v4.4 (2 domains)

Domain ID domain_id2vivA01
Class class2 — Mainly Beta
Architecture architecture40 — Beta Barrel
Topology topology10 — Thrombin, subunit H
Homologous superfamily homologous superfamily10 — Trypsin-like serine proteases
Domain ID domain_id2vivA02
Class class2 — Mainly Beta
Architecture architecture40 — Beta Barrel
Topology topology10 — Thrombin, subunit H
Homologous superfamily homologous superfamily10 — Trypsin-like serine proteases

8. Citations (1)

9. Files and Curves (10)