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- PDB-12cw: D189K thrombin inhibited with D-Phe-Pro-Arg-Chloromethylketone -

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Basic information

Entry
Database: PDB / ID: 12cw
TitleD189K thrombin inhibited with D-Phe-Pro-Arg-Chloromethylketone
Components
  • Thrombin heavy chain
  • Thrombin light chain
KeywordsBLOOD CLOTTING / serine protease / inhibitor
Function / homology
Function and homology information


negative regulation of astrocyte differentiation / thrombospondin receptor activity / thrombin / thrombin-activated receptor signaling pathway / Defective factor XII causes hereditary angioedema / regulation of blood coagulation / neutrophil-mediated killing of gram-negative bacterium / positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway / Platelet Aggregation (Plug Formation) / Defective F8 cleavage by thrombin ...negative regulation of astrocyte differentiation / thrombospondin receptor activity / thrombin / thrombin-activated receptor signaling pathway / Defective factor XII causes hereditary angioedema / regulation of blood coagulation / neutrophil-mediated killing of gram-negative bacterium / positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway / Platelet Aggregation (Plug Formation) / Defective F8 cleavage by thrombin / positive regulation of collagen biosynthetic process / Fibrin formation / negative regulation of platelet activation / negative regulation of blood coagulation / negative regulation of fibrinolysis / positive regulation of blood coagulation / negative regulation of proteolysis / Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus / fibrinolysis / Gamma-carboxylation of protein precursors / Amplification and propagation of coagulation cascade / Removal of aminoterminal propeptides from gamma-carboxylated proteins / Initiation of coagulation cascade / regulation of cytosolic calcium ion concentration / negative regulation of cytokine production involved in inflammatory response / Regulation of clotting cascade / Regulation of Complement cascade / positive regulation of receptor signaling pathway via JAK-STAT / positive regulation of release of sequestered calcium ion into cytosol / Cell surface interactions at the vascular wall / growth factor activity / Peptide ligand-binding receptors / response to wounding / lipopolysaccharide binding / platelet activation / positive regulation of protein localization to nucleus / Golgi lumen / blood coagulation / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / positive regulation of reactive oxygen species metabolic process / heparin binding / Thrombin signalling through proteinase activated receptors (PARs) / Dengue Virus-Host Interactions / antimicrobial humoral immune response mediated by antimicrobial peptide / blood microparticle / extracellular matrix / G alpha (q) signalling events / cell surface receptor signaling pathway / receptor ligand activity / endoplasmic reticulum lumen / serine-type endopeptidase activity / signaling receptor binding / calcium ion binding / proteolysis / extracellular exosome / extracellular region / plasma membrane
Similarity search - Function
Prothrombin/thrombin / Thrombin light chain / Thrombin light chain domain superfamily / : / Thrombin light chain / Kringle domain / Kringle / Kringle, conserved site / Kringle superfamily / Kringle domain signature. ...Prothrombin/thrombin / Thrombin light chain / Thrombin light chain domain superfamily / : / Thrombin light chain / Kringle domain / Kringle / Kringle, conserved site / Kringle superfamily / Kringle domain signature. / Kringle domain profile. / Kringle domain / Vitamin K-dependent carboxylation/gamma-carboxyglutamic (GLA) domain / Gamma-carboxyglutamic acid-rich (GLA) domain / Gamma-carboxyglutamic acid-rich (GLA) domain superfamily / Vitamin K-dependent carboxylation domain. / Gla domain profile. / Domain containing Gla (gamma-carboxyglutamate) residues. / Kringle-like fold / Serine proteases, trypsin family, histidine active site / Serine proteases, trypsin family, serine active site / Serine proteases, trypsin family, histidine active site. / Serine proteases, trypsin family, serine active site. / Peptidase S1A, chymotrypsin family / Serine proteases, trypsin domain profile. / Trypsin-like serine protease / Serine proteases, trypsin domain / Trypsin / Peptidase S1, PA clan
Similarity search - Domain/homology
Chem-0G6 / Prothrombin
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.6 Å
AuthorsFriet, T. / Mohammed, B.M. / Sukumar, N. / Di Cera, E.
Funding support United States, 3items
OrganizationGrant numberCountry
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)HL049413, HL139554, HL147821 United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)P30GM133893 United States
Department of Energy (DOE, United States)KP1607011 United States
CitationJournal: J.Thromb.Haemost. / Year: 2026
Title: Structural analysis of the primary specificity of thrombin.
Authors: Friet, T. / Mikhail, G. / Mohammed, B.M. / Pelc, L.A. / Dei Rossi, A. / Korolev, S. / Di Cera, E.
History
DepositionMar 27, 2026Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 7, 2026Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Thrombin light chain
B: Thrombin heavy chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)37,5343
Polymers37,0802
Non-polymers4541
Water2,828157
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3350 Å2
ΔGint-14 kcal/mol
Surface area14610 Å2
MethodPISA
Unit cell
Length a, b, c (Å)117.175, 117.175, 58.097
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number92
Space group name H-MP41212
Space group name HallP4abw2nw
Symmetry operation#1: x,y,z
#2: -y+1/2,x+1/2,z+1/4
#3: y+1/2,-x+1/2,z+3/4
#4: x+1/2,-y+1/2,-z+3/4
#5: -x+1/2,y+1/2,-z+1/4
#6: -x,-y,z+1/2
#7: y,x,-z
#8: -y,-x,-z+1/2

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Components

#1: Protein/peptide Thrombin light chain


Mass: 5641.175 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: F2 / Production host: Mesocricetus auratus (golden hamster) / References: UniProt: P00734
#2: Protein Thrombin heavy chain


Mass: 31439.127 Da / Num. of mol.: 1 / Mutation: D519K
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: F2 / Production host: Mesocricetus auratus (golden hamster) / References: UniProt: P00734
#3: Chemical ChemComp-0G6 / D-phenylalanyl-N-[(2S,3S)-6-{[amino(iminio)methyl]amino}-1-chloro-2-hydroxyhexan-3-yl]-L-prolinamide / PPACK


Type: peptide-like / Mass: 453.986 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C21H34ClN6O3 / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 157 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

CrystalDensity Matthews: 2.76 Å3/Da / Density % sol: 55.5 %
Crystal growTemperature: 293.15 K / Method: vapor diffusion, hanging drop
Details: 0.2 M Ammonium sulfate, 0.1 M Tris pH 8.5, 25% w/v Polyethylene glycol 3,350

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: NSLS-II / Beamline: 17-ID-2 / Wavelength: 0.97933 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Mar 4, 2025
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97933 Å / Relative weight: 1
ReflectionResolution: 1.55→82.86 Å / Num. obs: 58642 / % possible obs: 100 % / Redundancy: 26.9 % / Biso Wilson estimate: 19.77 Å2 / CC1/2: 1 / Rmerge(I) obs: 0.128 / Rpim(I) all: 0.025 / Rrim(I) all: 0.131 / Χ2: 0.86 / Net I/σ(I): 17.8 / Num. measured all: 1578317
Reflection shellResolution: 1.55→1.64 Å / % possible obs: 100 % / Redundancy: 27.3 % / Rmerge(I) obs: 2.663 / Num. measured all: 229980 / Num. unique obs: 8434 / CC1/2: 0.455 / Rpim(I) all: 0.518 / Rrim(I) all: 2.714 / Χ2: 0.71 / Net I/σ(I) obs: 1.6

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Processing

Software
NameVersionClassificationNB
PHENIX1.21.2_5419refinement
Aimlessdata scaling
XDSdata reduction
PHASERphasing
PDB_EXTRACTdata extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.6→41.43 Å / SU ML: 0.1937 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 22.0726
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.229 2642 4.93 %
Rwork0.2124 50956 -
obs0.2132 53598 99.61 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 24.65 Å2
Refinement stepCycle: LAST / Resolution: 1.6→41.43 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2540 0 0 157 2697
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00622605
X-RAY DIFFRACTIONf_angle_d0.88863518
X-RAY DIFFRACTIONf_chiral_restr0.0588361
X-RAY DIFFRACTIONf_plane_restr0.0109455
X-RAY DIFFRACTIONf_dihedral_angle_d16.5733975
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.6-1.630.35311310.31362522X-RAY DIFFRACTION94.38
1.63-1.660.32431210.30792616X-RAY DIFFRACTION98.6
1.66-1.690.2571390.28032632X-RAY DIFFRACTION100
1.69-1.730.30251310.26772659X-RAY DIFFRACTION99.89
1.73-1.770.24391370.24762664X-RAY DIFFRACTION100
1.77-1.820.25781520.23282662X-RAY DIFFRACTION100
1.82-1.860.24391260.21942647X-RAY DIFFRACTION100
1.86-1.920.23171780.22332623X-RAY DIFFRACTION99.89
1.92-1.980.26051460.22442656X-RAY DIFFRACTION100
1.98-2.050.24321330.21832662X-RAY DIFFRACTION100
2.05-2.130.26711530.20862672X-RAY DIFFRACTION100
2.13-2.230.25771210.21522706X-RAY DIFFRACTION100
2.23-2.350.23431400.2152673X-RAY DIFFRACTION99.96
2.35-2.50.27391280.22062700X-RAY DIFFRACTION100
2.5-2.690.23161470.22272695X-RAY DIFFRACTION100
2.69-2.960.23011430.22172718X-RAY DIFFRACTION100
2.96-3.390.23141530.21532727X-RAY DIFFRACTION100
3.39-4.270.19791240.17842791X-RAY DIFFRACTION100
4.27-41.430.17021390.18652931X-RAY DIFFRACTION99.87

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