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- PDB-6tkh: Tsetse thrombin inhibitor in complex with human alpha-thrombin - ... -

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Open data


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Basic information

Entry
Database: PDB / ID: 6tkh
TitleTsetse thrombin inhibitor in complex with human alpha-thrombin - orthorhombic form at 7keV
Components
  • Thrombin heavy chain
  • Thrombin light chain
  • Tsetse thrombin inhibitor
KeywordsBLOOD CLOTTING / anticoagulant tyrosine sulfation posttranslational modification complex
Function / homology
Function and homology information


positive regulation of lipid kinase activity / positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway / cytolysis by host of symbiont cells / thrombospondin receptor activity / Defective factor XII causes hereditary angioedema / thrombin / regulation of blood coagulation / neutrophil-mediated killing of gram-negative bacterium / ligand-gated ion channel signaling pathway / Defective F8 cleavage by thrombin ...positive regulation of lipid kinase activity / positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway / cytolysis by host of symbiont cells / thrombospondin receptor activity / Defective factor XII causes hereditary angioedema / thrombin / regulation of blood coagulation / neutrophil-mediated killing of gram-negative bacterium / ligand-gated ion channel signaling pathway / Defective F8 cleavage by thrombin / Platelet Aggregation (Plug Formation) / negative regulation of astrocyte differentiation / negative regulation of platelet activation / positive regulation of collagen biosynthetic process / negative regulation of cytokine production involved in inflammatory response / positive regulation of blood coagulation / negative regulation of fibrinolysis / Gamma-carboxylation of protein precursors / Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus / Common Pathway of Fibrin Clot Formation / Removal of aminoterminal propeptides from gamma-carboxylated proteins / fibrinolysis / regulation of cytosolic calcium ion concentration / Intrinsic Pathway of Fibrin Clot Formation / Peptide ligand-binding receptors / positive regulation of release of sequestered calcium ion into cytosol / acute-phase response / Regulation of Complement cascade / negative regulation of proteolysis / Cell surface interactions at the vascular wall / lipopolysaccharide binding / positive regulation of receptor signaling pathway via JAK-STAT / growth factor activity / serine-type endopeptidase inhibitor activity / positive regulation of insulin secretion / platelet activation / response to wounding / positive regulation of protein localization to nucleus / Golgi lumen / antimicrobial humoral immune response mediated by antimicrobial peptide / 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 / blood coagulation / Thrombin signalling through proteinase activated receptors (PARs) / heparin binding / regulation of cell shape / positive regulation of cell growth / G alpha (q) signalling events / collagen-containing extracellular matrix / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / cell surface receptor signaling pathway / blood microparticle / positive regulation of protein phosphorylation / G protein-coupled receptor signaling pathway / endoplasmic reticulum lumen / serine-type endopeptidase activity / signaling receptor binding / calcium ion binding / positive regulation of cell population proliferation / proteolysis / extracellular space / 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. / Kringle domain profile. ...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 / Peptidase S1A, chymotrypsin family / Serine proteases, trypsin family, histidine active site. / Serine proteases, trypsin domain profile. / Serine proteases, trypsin family, serine active site. / Trypsin-like serine protease / Serine proteases, trypsin domain / Trypsin / Peptidase S1, PA clan, chymotrypsin-like fold / Peptidase S1, PA clan
Similarity search - Domain/homology
Tsetse thrombin inhibitor / Prothrombin
Similarity search - Component
Biological speciesHomo sapiens (human)
Glossina morsitans morsitans (fry)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.9 Å
AuthorsCalisto, B.M. / Ripoll-Rozada, J. / de Sanctis, D. / Pereira, P.J.B.
Funding support Australia, Portugal, 2items
OrganizationGrant numberCountry
National Health and Medical Research Council (Australia)APP1120941 Australia
Fundacao para a Ciencia e a Tecnologia57/2016/CP1355/CT0011 Portugal
CitationJournal: Cell Chem Biol / Year: 2021
Title: Sulfotyrosine-Mediated Recognition of Human Thrombin by a Tsetse Fly Anticoagulant Mimics Physiological Substrates.
Authors: Calisto, B.M. / Ripoll-Rozada, J. / Dowman, L.J. / Franck, C. / Agten, S.M. / Parker, B.L. / Veloso, R.C. / Vale, N. / Gomes, P. / de Sanctis, D. / Payne, R.J. / Pereira, P.J.B.
History
DepositionNov 28, 2019Deposition site: PDBE / Processing site: PDBE
Revision 1.0Nov 4, 2020Provider: repository / Type: Initial release
Revision 1.1Feb 3, 2021Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.year
Revision 1.2Jan 24, 2024Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
L: Thrombin light chain
H: Thrombin heavy chain
I: Tsetse thrombin inhibitor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)40,2687
Polymers39,8403
Non-polymers4284
Water3,045169
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area6870 Å2
ΔGint-33 kcal/mol
Surface area13080 Å2
MethodPISA
Unit cell
Length a, b, c (Å)46.437, 81.045, 85.338
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Space group name HallP2ac2ab
Symmetry operation#1: x,y,z
#2: x+1/2,-y+1/2,-z
#3: -x,y+1/2,-z+1/2
#4: -x+1/2,-y,z+1/2

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Components

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Protein , 2 types, 2 molecules HI

#2: Protein Thrombin heavy chain / Coagulation factor II


Mass: 29780.219 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P00734, thrombin
#3: Protein Tsetse thrombin inhibitor


Mass: 5962.750 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Glossina morsitans morsitans (fry) / References: UniProt: O97373

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Protein/peptide / Sugars , 2 types, 2 molecules L

#1: Protein/peptide Thrombin light chain / Coagulation factor II


Mass: 4096.534 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P00734, thrombin
#5: Sugar ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0

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Non-polymers , 3 types, 172 molecules

#4: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C3H8O3
#6: Chemical ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Na
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 169 / Source method: isolated from a natural source / Formula: H2O

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Details

Has ligand of interestY

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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: 2.33 Å3/Da / Density % sol: 47.3 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop
Details: 0.1 M HEPES pH 7.5, 0.2 M ammonium acetate, 25 % (w/v) PEG 3350

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID23-1 / Wavelength: 1.771 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Sep 2, 2015
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.771 Å / Relative weight: 1
ReflectionResolution: 1.9→58.8 Å / Num. obs: 24586 / % possible obs: 95.3 % / Redundancy: 12.4 % / Biso Wilson estimate: 27.73 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.078 / Net I/σ(I): 19.8
Reflection shellResolution: 1.9→2.01 Å / Redundancy: 12 % / Rmerge(I) obs: 0.714 / Mean I/σ(I) obs: 3.8 / Num. unique obs: 3234 / CC1/2: 0.879 / % possible all: 87.9

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Processing

Software
NameVersionClassification
PHENIX1.16_3549refinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3U69

3u69


Resolution: 1.9→42.67 Å / SU ML: 0.1739 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 20.5796
RfactorNum. reflection% reflection
Rfree0.2003 1278 5.21 %
Rwork0.1606 --
obs0.1626 24536 94.76 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso mean: 37.11 Å2
Refinement stepCycle: LAST / Resolution: 1.9→42.67 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2511 0 21 169 2701
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00512613
X-RAY DIFFRACTIONf_angle_d0.81093532
X-RAY DIFFRACTIONf_chiral_restr0.0556365
X-RAY DIFFRACTIONf_plane_restr0.0053458
X-RAY DIFFRACTIONf_dihedral_angle_d23.07381572
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.9-1.980.25281200.22282306X-RAY DIFFRACTION86.21
1.98-2.070.2631360.18892415X-RAY DIFFRACTION90.11
2.07-2.180.19891410.17022482X-RAY DIFFRACTION92.36
2.18-2.320.24321490.1692516X-RAY DIFFRACTION93.87
2.32-2.50.1981280.1692610X-RAY DIFFRACTION96.41
2.5-2.750.21821340.16292673X-RAY DIFFRACTION97.47
2.75-3.140.19531610.16262670X-RAY DIFFRACTION98.13
3.14-3.960.16761530.14582697X-RAY DIFFRACTION98.24
3.96-42.670.19651560.15362889X-RAY DIFFRACTION99.51
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
14.874035012090.6552486093875.607120642670.5674699257890.6258875678557.02930232534-0.01810108757540.151689526021-0.0676034450411-0.336812914950.194497065935-0.93283647545-0.1969986031760.737861250241-0.1951269869970.368271031761-0.0387937460610.07395881497490.353768666498-0.03093578281730.4665886804926.671614491858.42186505153-24.4255358344
25.08401070305-0.911782397528-5.099042144953.39382556090.9418818859055.154479236260.4398911926860.8257270768410.732371100456-0.2679892013570.1195678796460.252450342694-1.1858686223-0.517019979528-0.4441274924050.5271508016960.04149472517390.03128352195680.3875188762150.06465283461190.209023369924-5.3869895191912.2724817398-30.7488307981
33.92247936427-3.91261917119-3.038790487484.311537875123.302227020922.571795814890.1748694025190.04613120915030.877158132442-0.459358696577-0.3871259305470.0936542432246-0.925304922174-0.3136186177930.04552962537470.4574572243430.05356654961980.02477237141240.3087320291460.01850674440380.387948261138-9.5571247870622.5409089076-18.9859352677
41.9937227493-0.461219125163-0.9931697075151.633343376090.05901495192011.71969036281-0.2225670758810.0809165292734-0.262035075968-0.05204862680460.1829541754710.08864789107220.413704269091-0.4034525304290.003985109977070.344383959284-0.04506245246460.02407327402470.20741496288-0.02072252838840.249726897787-7.21262068347-3.1980721926-19.4145343273
50.883253199383-1.138163698220.8126680463343.475875079850.9016321301945.37213872063-0.317248190629-0.330245762651-0.342700435747-0.05280776826790.0771322050703-0.3384266592340.7435153290860.5525920915460.3165407107570.2878839694350.0794736122150.05811270504450.226408038662-0.01023320360510.2853794679972.55927059695-3.71166594265-13.3030418471
60.642079902516-0.419386955206-1.561429354980.3125213432451.190351064234.18345383246-0.932528469976-0.0461938819128-0.6907763868540.0202302225728-0.212048897706-0.02792880880831.650904794890.52194316340.4904932732150.6252675479580.1550093791240.1840249055880.2605635462350.06308920511270.438271748151-0.195873941666-11.6233207549-7.17598244011
73.35810782986-0.1345879354851.132834397522.833966652370.4317871037653.81444638448-0.0606620593960.0273126042585-0.470362311646-0.4962370521670.123693795026-0.074522640970.5593047904920.111724155402-0.1273202490530.3581773698110.05393858198340.08741030313970.211558869761-0.003581235566660.2916742900450.234099702328-9.58013899439-22.0378698527
86.675355454820.934810391327-4.954103089777.02439888469-1.973314764856.425576137050.0710291798225-0.6872758775660.1436755928210.502478704833-0.259376945441-0.389715844267-0.1548964777310.8615220414050.1868753092030.2668726010330.086976607542-0.0137418095420.353017841230.04149209436970.1979915136352.520551958220.07440809675722.84495291151
91.65187828418-0.22682079982-0.9752817725482.419308155770.3879807532332.45132093209-0.05596988256630.03828284683550.0660020664941-0.1615257823730.0851204538105-0.340559812002-0.0955511717480.383742859942-0.06248380353940.215650038405-0.01078016811940.03690808849280.2400863542240.005219255889310.2253271588542.834026370087.09757736194-17.7892467087
101.2395500055-0.597992580615-0.8726986996360.8224241335930.2390340831433.359805631470.0379219755227-0.0345103826382-0.05026343240760.0466720942193-0.0564634156460.0946759865272-0.0315473541015-0.468506856337-0.007254242795110.2008525514870.008262061829270.007909913638460.2308407501660.02552512791870.217995011965-13.23435284165.02627072886-10.8562568449
113.846320025510.357770148853-0.1887190061662.24478487577-0.17760629435.97606982753-0.0244986989174-0.3581429788860.279552056350.2755022838220.14648290286-0.0300769652375-0.522457050093-0.199154180456-0.06000994506710.2498664866830.02679571963720.0401559092090.167353302482-0.02005809022550.192838231632-10.042729403711.4655461631-0.796994114645
122.28983365503-3.06984051937-1.092498708767.838853219191.900214253025.51500269639-0.0876988410577-0.21202251824-0.1103760715690.1722626252490.1350612996020.5826561870770.236392777428-0.701384034833-0.01258153525940.1957364747810.0002980270440030.01011773815930.2506169946320.02468197768750.243076960862-13.83638305513.38410317195-10.6331745899
131.66263646347-0.449648896489-0.7889209372422.78694618342-0.2158087815263.46532283807-0.0356786582655-0.09048166113120.1447283583890.01022313550430.0674278246249-0.00821100915115-0.198719245198-0.0773571872122-0.04906397999510.2064034620010.007034337607070.001895566436550.149441609888-0.008442079577960.174692098881-5.518031375799.72073702879-10.9458472866
148.69676210105-6.13164637761-2.839163535258.687291735722.69958333453.80519198945-0.341512522002-0.4415961968190.3223159314340.0861944211950.204503182578-1.09067748896-0.1139488325391.53118098779-0.04281646328640.261379462150.04831537668460.007807766418770.5971681172920.05803559404850.39011342750513.10841577144.9524002861-7.92572838101
153.540873017333.37695651488-3.551322505594.69765962313-5.830693689977.86181980540.162199632758-0.70419725159-0.274182254480.599279177518-0.826559825599-0.875276213216-0.6003410406721.314520212690.3871342078090.403299599326-0.0352974287399-0.0436484412820.491568521233-0.02343670765980.4572840290393.7273626356312.58764800050.260574045164
164.09647078140.3552740600190.1572363858823.8370425511-1.86557814666.18545607851-0.3697310234070.469632294799-0.131093646405-0.3774104424090.473525346356-0.08872859813420.566460390149-0.0956280640492-0.1525811357370.3520786745650.001448238487990.03478266850850.256149164002-0.0166060492850.199081490386-12.1337013738-2.009113282943.35148719924
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'L' and (resid 285 through 299 )
2X-RAY DIFFRACTION2chain 'L' and (resid 300 through 308 )
3X-RAY DIFFRACTION3chain 'L' and (resid 309 through 320 )
4X-RAY DIFFRACTION4chain 'H' and (resid 321 through 344 )
5X-RAY DIFFRACTION5chain 'H' and (resid 345 through 365 )
6X-RAY DIFFRACTION6chain 'H' and (resid 366 through 383 )
7X-RAY DIFFRACTION7chain 'H' and (resid 384 through 406 )
8X-RAY DIFFRACTION8chain 'H' and (resid 407 through 420 )
9X-RAY DIFFRACTION9chain 'H' and (resid 421 through 460 )
10X-RAY DIFFRACTION10chain 'H' and (resid 461 through 495 )
11X-RAY DIFFRACTION11chain 'H' and (resid 496 through 514 )
12X-RAY DIFFRACTION12chain 'H' and (resid 515 through 527 )
13X-RAY DIFFRACTION13chain 'H' and (resid 528 through 563 )
14X-RAY DIFFRACTION14chain 'H' and (resid 564 through 578 )
15X-RAY DIFFRACTION15chain 'I' and (resid 1 through 23 )
16X-RAY DIFFRACTION16chain 'I' and (resid 24 through 31 )

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