Literature summary for 3.4.21.5 extracted from

Koh, C.Y.; Kumar, S.; Kazimirova, M.; Nuttall, P.A.; Radhakrishnan, U.P.; Kim, S.; Jagadeeswaran, P.; Imamura, T.; Mizuguchi, J.; Iwanaga, S.; Swaminathan, K.; Kini, R.M.
Crystal structure of thrombin in complex with s-variegin: insights of a novel mechanism of inhibition and design of tunable thrombin inhibitors (2011), PLoS ONE, 6, e26367.

Crystallization (Commentary)

Crystallization (Comment)	Organism
alpha-thrombin complexed with synthetic variegin, hanging drop vapor diffusion method, 0.001 ml of protein solution, containing 20 mg/ml protein, 3 mg/ml variegin inhibitor, 50 mM HEPES, pH 7.5, and 375 mM NaCl, is mixed with 0.001 ml of precipitant solution, containing 100 mM HEPES, pH 7.4, and 20-25% PEG 8000, and equilibrated against 1 ml of the precipitant solution, 4°C, X-ray diffraction structure determination and analysis at 2.4 A resolution, modeling	Homo sapiens

Crystallization (Comment)

Organism

alpha-thrombin complexed with synthetic variegin, hanging drop vapor diffusion method, 0.001 ml of protein solution, containing 20 mg/ml protein, 3 mg/ml variegin inhibitor, 50 mM HEPES, pH 7.5, and 375 mM NaCl, is mixed with 0.001 ml of precipitant solution, containing 100 mM HEPES, pH 7.4, and 20-25% PEG 8000, and equilibrated against 1 ml of the precipitant solution, 4°C, X-ray diffraction structure determination and analysis at 2.4 A resolution, modeling

Homo sapiens

Inhibitors

Inhibitors	Comment	Organism
DV23	i.e. SDQGDVAEPKMHKTAPPFDFEAIPEEYLDDES, a variegin variant, a fast, tight-binding, competitive inhibitor	Homo sapiens
DV23K10R	i.e. SDQGDVAEPRMHKTAPPFDFEAIPEEYLDDES, a variegin variant, a fast, tight-binding, competitive inhibitor	Homo sapiens
DV24	i.e. SDQGDVAEPKMHKTAPPFDFEAIPEEYLDDES, a variegin variant, a fast, tight-binding, competitive inhibitor	Homo sapiens
DV24H12A	i.e. SDQGDVAEPKMAKTAPPFDFEAIPEEYLDDES, a variegin variant, a fast, tight-binding, competitive inhibitor	Homo sapiens
DV24K10R	i.e. SDQGDVAEPRMHKTAPPFDFEAIPEEYLDDES, a variegin variant, a fast, tight-binding, competitive inhibitor	Homo sapiens
DV24K10RY	-	Homo sapiens
DV24K10RYphos	i.e. SDQGDVAEPRMHKTAPPFDFEAIPEEYphosLDDES, a variegin variant, a fast, tight-binding, competitive inhibitor	Homo sapiens
DV24K10RYsulf	i.e. SDQGDVAEPRMHKTAPPFDFEAIPEEYsulfLDDE, a variegin variant, a fast, tight-binding, competitive inhibitor	Homo sapiens
DV24Yphos	i.e. SDQGDVAEPKMHKTAPPFDFEAIPEEYphosLDDE, a variegin variant, a fast, tight-binding, competitive inhibitor	Homo sapiens
DV24Ysulf	i.e. SDQGDVAEPKMHKTAPPFDFEAIPEEYsulfLDDE, a variegin variant, a fast, tight-binding, competitive inhibitor	Homo sapiens
EP21	i.e. SDQGDVAEPKMHKTAPPFDFEAIPEEYLDDES, a variegin variant, a slow, tight-binding, competitive inhibitor	Homo sapiens
EP25	i.e. SDQGDVAEPKMHKTAPPFDFEAIPEEYLDDES, a variegin variant, a slow, tight-binding, competitive inhibitor	Homo sapiens
EP25A22E	i.e. SDQGDVAEPKMHKTAPPFDFEEIPEEYLDDES, a variegin variant, a fast, tight-binding, competitive inhibitor	Homo sapiens
hirulog-1	i.e. bivalirudin or DFPRPGGGGNGDFEEIPEEYL, a variegin variant, a fast, tight-binding, competitive inhibitor	Homo sapiens
MH18	i.e. SDQGDVAEPKMHKTAPPFDFEAIPEEYLDDES, a variegin variant, a fast, tight-binding, noncompetitive inhibitor	Homo sapiens
MH18H12A	i.e. SDQGDVAEPKMAKTAPPFDFEAIPEEYLDDES, a variegin variant, a fast, tight-binding, noncompetitive inhibitor	Homo sapiens
MH18Ysulf	i.e. SDQGDVAEPKMHKTAPPFDFEAIPEEYsulfLDDES, a variegin variant, a fast, tight-binding, noncompetitive inhibitor	Homo sapiens
MH22	i.e. SDQGDVAEPKMHKTAPPFDFEAIPEEYLDDES, a variegin variant, a fast, tight-binding, noncompetitive inhibitor	Homo sapiens
MH22A22E	i.e. SDQGDVAEPKMHKTAPPFDFEEIPEEYLDDES, a variegin variant, a fast, tight-binding, noncompetitive inhibitor	Homo sapiens
additional information	mechanism of inhibition and design of tunable thrombin inhibitors, structure-based design of 17 variegin variants, differing in potency, kinetics and mechanism of inhibition, in vivo antithrombotic effects of the variegin variants correlate well with their in vitro affinities for thrombin, overview	Homo sapiens
variegin	i.e. SDQGDVAEPKMHKTAPPFDFEAIPEEYLDDES, isolated from the tropical bont tick, the molecule exhibits a unique two-modes inhibitory property on thrombin active site, i.e. competitive before cleavage, noncompetitive after cleavage, overview. Mechanism of thrombin inhibition by disrupting the charge relay system, a fast, tight-binding, competitive inhibitor	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
commercial preparation	lyophilized, recombinant	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
S2238 + H2O	a chromogenic substrate	Homo sapiens	?	-	?

Ki Value [mM]

Ki Value [mM]	Ki Value maximum [mM]	Inhibitor	Comment	Organism
0.00000004	-	DV24K10RY	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens
0.00000006	-	DV24Ysulf	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens
0.00000015	-	DV24K10RY	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens
0.00000026	-	DV24K10RY	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens
0.00000031	-	DV24	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens
0.00000031	-	EP25A22E	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens
0.00000032	-	EP21	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens
0.00000032	-	variegin	synthetic molecule, pH and temperature not specified in the publication, after no preincubation time	Homo sapiens
0.00000033	-	DV24Yphos	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens
0.00000037	-	EP25	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens
0.0000006	-	DV23K10R	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens
0.00000125	-	MH18Ysulf	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens
0.0000022	-	DV23	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens
0.0000023	-	hirulog-1	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens
0.0000032	-	DV24H12A	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens
0.0000141	-	MH22	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens
0.0000149	-	MH18	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens
0.0000151	-	MH22A22E	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens
0.000329	-	MH18H12A	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor
0.0000012	-	pH and temperature not specified in the publication, after 20 min preincubation	Homo sapiens	MH18Ysulf
0.0000013	-	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens	MH18Ysulf
0.0000014	-	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens	DV24K10RY
0.0000017	-	pH and temperature not specified in the publication, after 20 min preincubation	Homo sapiens	DV24K10RY
0.0000017	-	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens	DV24Ysulf
0.000002	-	pH and temperature not specified in the publication, after 20 min preincubation	Homo sapiens	DV24Ysulf
0.0000046	-	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens	DV24K10RY
0.000007	-	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens	DV24K10RYphos
0.0000075	-	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens	DV24
0.0000078	-	pH and temperature not specified in the publication, after 20 min preincubation	Homo sapiens	DV24K10RY
0.00000825	-	synthetic molecule, pH and temperature not specified in the publication, after no preincubation time	Homo sapiens	variegin
0.0000087	-	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens	DV24Yphos
0.0000101	-	pH and temperature not specified in the publication, after 20 min preincubation	Homo sapiens	DV24
0.0000104	-	synthetic molecule, pH and temperature not specified in the publication, after 20 min preincubation	Homo sapiens	variegin
0.0000109	-	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens	MH18
0.0000115	-	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens	MH22
0.0000117	-	pH and temperature not specified in the publication, after 20 min preincubation	Homo sapiens	MH18
0.000012	-	pH and temperature not specified in the publication, after 20 min preincubation	Homo sapiens	DV24K10RYphos
0.0000123	-	pH and temperature not specified in the publication, after 20 min preincubation	Homo sapiens	MH22
0.0000124	-	pH and temperature not specified in the publication, after 20 min preincubation	Homo sapiens	DV24Yphos
0.0000129	-	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens	DV23K10R
0.0000131	-	pH and temperature not specified in the publication, after 20 min preincubation	Homo sapiens	EP25
0.0000135	-	pH and temperature not specified in the publication, after 20 min preincubation	Homo sapiens	EP25A22E
0.0000136	-	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens	MH22A22E
0.0000156	-	pH and temperature not specified in the publication, after 20 min preincubation	Homo sapiens	MH22A22E
0.0000162	-	pH and temperature not specified in the publication, after 20 min preincubation	Homo sapiens	EP21
0.0000454	-	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens	DV23
0.0000482	-	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens	DV24H12A
0.0000726	-	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens	hirulog-1
0.0000778	-	pH and temperature not specified in the publication, after 20 min preincubation	Homo sapiens	DV23
0.000102	-	pH and temperature not specified in the publication, after 20 min preincubation	Homo sapiens	hirulog-1
0.000102	-	pH and temperature not specified in the publication, after 20 min preincubation	Homo sapiens	DV23K10R
0.000124	-	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens	EP25A22E
0.000141	-	pH and temperature not specified in the publication, after 20 min preincubation	Homo sapiens	DV24H12A
0.000173	-	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens	EP25
0.000177	-	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens	EP21
0.000328	-	pH and temperature not specified in the publication, after no preincubation time	Homo sapiens	MH18H12A
0.000343	-	pH and temperature not specified in the publication, after 20 min preincubation	Homo sapiens	MH18H12A

General Information

General Information	Comment	Organism
additional information	the thrombin catalytic triad comprises residues His57, Asp102, and Ser195	Homo sapiens