EzCatDB M00155

EzCatDB: M00155

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DB code	M00155
RLCP classification	1.13.30000.10 : Hydrolysis
CATH domain	Domain 1	2.10.70.10 : Complement Module; domain 1
	Domain 2	2.10.25.10 : Laminin
	Domain 3	2.40.20.10 : Plasminogen Kringle 4
	Domain 4	2.40.10.10 : Thrombin, subunit H		Catalytic domain
	Domain 5	2.40.10.10 : Thrombin, subunit H		Catalytic domain
E.C.	3.4.21.68
CSA	1rtf

CATH domain	Related DB codes (homologues)
2.10.25.10 : Laminin	M00139,M00133,M00212,M00152,M00315,M00316
2.10.70.10 : Complement Module; domain 1	M00139,M00315,M00316
2.40.10.10 : Thrombin, subunit H	M00139,D00214,M00167,D00426,M00133,D00428,D00429,D00430,D00431,D00432,D00433,D00434,D00435,M00227,M00209,D00194,D00197,D00211,D00212,D00216,M00212,D00224,D00497,M00217,M00216,D00528,D00848,D00850,D00851,D00852,D00855,M00152,M00157,M00181,M00315,M00316,M00317,M00348,M00349,T00074,T00410,T00411
2.40.20.10 : Plasminogen Kringle 4	M00152,M00157

Enzyme Name
UniProtKB			KEGG
	P00750	P98119	KEGG
Protein name	Tissue-type plasminogen activator (t-PA) (t-plasminogen activator) (tPA) (EC 3.4.21.68)AltName: INN=Alteplase;AltName: INN=Reteplase;	Salivary plasminogen activator alpha 1	t-plasminogen activator tissue plasminogen activator plasminogen activator, tissue-type tissue-type plasminogen activator tPA t-PA
Synonyms	None	EC 3.4.21.68 DSPA alpha-1
Contains	Tissue-type plasminogen activator chain A Tissue-type plasminogen activator chain B	None
RefSeq	NP_000921.1 (Protein) NM_000930.3 (DNA/RNA sequence) NP_127509.1 (Protein) NM_033011.2 (DNA/RNA sequence)
MEROPS	S01.232 (Serine)	S01.239 (Serine)
Pfam	PF00008 (EGF) PF00039 (fn1) PF00051 (Kringle) PF00089 (Trypsin) [Graphical view]	PF00008 (EGF) PF00039 (fn1) PF00051 (Kringle) PF00089 (Trypsin) [Graphical view]

UniProtKB:Accession Number	P00750	P98119
Entry name	TPA_HUMAN	URT1_DESRO
Activity	Specific cleavage of Arg-\|-Val bond in plasminogen to form plasmin.	Specific cleavage of Arg-\|-Val bond in plasminogen to form plasmin.
Subunit	Heterodimer of chain A and chain B held by a disulfide bond. Binds to fibrin with high affinity. This interaction leads to an increase in the catalytic efficiency of the enzyme between 100-fold and 1000-fold, due to an increase in affinity for plasminogen. Similarly, binding to heparin increases the activation of plasminogen. Binds to annexin A2, cytokeratin-8, fibronectin and laminin. Binds to mannose receptor and the low- density lipoprotein receptor-related protein (LRP1), these proteins are involved in TPA clearance. Yet unidentified interactions on endothelial cells and vascular smooth muscle cells (VSMC) lead to a 100-fold stimulation of plasminogen activation. In addition, binding to VSMC reduces TPA inhibition by PAI-1 by 30-fold. Binds LRP1B, binding is followed by internalization and degradation.	Monomer.
Subcellular location	Secreted, extracellular space.	Secreted.
Cofactor

Compound table: links to PDB-related databases & PoSSuM
								Substrates	Products	intermediates
KEGG-id								C00520	C00471	I00087		I00085		I00086
Compound								Plasminogen	Plasmin	Peptidyl-tetrahedral intermediate		Acyl-enzyme		Tetrahedral intermediate
Type								peptide/protein	peptide/protein
ChEBI
PubChem

1tpgA01								Unbound	Unbound	Unbound		Unbound		Unbound
1tpgA02								Unbound	Unbound	Unbound		Unbound		Unbound
1tpmA								Unbound	Unbound	Unbound		Unbound		Unbound
1tpnA								Unbound	Unbound	Unbound		Unbound		Unbound
1pk2A								Unbound	Unbound	Unbound		Unbound		Unbound
1pmlA								Unbound	Unbound	Unbound		Unbound		Unbound
1pmlB								Unbound	Unbound	Unbound		Unbound		Unbound
1pmlC								Unbound	Unbound	Unbound		Unbound		Unbound
1tpkA								Unbound	Unbound	Unbound		Unbound		Unbound
1tpkB								Unbound	Unbound	Unbound		Unbound		Unbound
1tpkC								Unbound	Unbound	Unbound		Unbound		Unbound
1a5hA01								Unbound	Unbound	Unbound		Unbound		Unbound
1a5hB01								Unbound	Unbound	Unbound		Unbound		Unbound
1a5iA01								Unbound	Unbound	Unbound		Unbound		Transition-state-analogue:GLU-GLY-ARG-CH2
1bdaA01								Unbound	Unbound	Unbound		Unbound		Transition-state-analogue:DSY-GLU-GLY-ARG-CH2
1bdaB01								Unbound	Unbound	Unbound		Unbound		Transition-state-analogue:DSY-GLU-GLY-ARG-CH2
1rtfB01								Unbound	Unbound	Unbound		Unbound		Unbound
1a5hA02								Unbound	Unbound	Unbound		Unbound		Unbound
1a5hB02								Unbound	Unbound	Unbound		Unbound		Unbound
1a5iA02								Unbound	Unbound	Unbound		Unbound		Unbound
1bdaA02								Unbound	Unbound	Unbound		Unbound		Unbound
1bdaB02								Unbound	Unbound	Unbound		Unbound		Unbound
1rtfB02								Unbound	Unbound	Unbound		Unbound		Unbound

Active-site residues
resource
Swoss-prot; P00750, P98119 & literature [21]
pdb								Catalytic residues	Cofactor-binding residues	Main-chain involved in catalysis	comment

1tpgA01
1tpgA02											`mutant C83S`
1tpmA
1tpnA
1pk2A
1pmlA									`ASN 26;LYS 33;VAL 34;TYR 35;HIS 64(Chloride binding)`
1pmlB									`ASN 26;LYS 33;VAL 34;TYR 35;HIS 64(Chloride binding)`
1pmlC									`ASN 26;LYS 33;VAL 34;TYR 35;HIS 64(Chloride binding)`
1tpkA									`ASN 26;LYS 33;VAL 34;TYR 35;HIS 64(Chloride binding)`
1tpkB									`ASN 26;LYS 33;VAL 34;TYR 35;HIS 64(Chloride binding)`
1tpkC									`ASN 26;LYS 33;VAL 34;TYR 35;HIS 64(Chloride binding)`
1a5hA01								`SER 195`		`GLY 193;SER 195`
1a5hB01								`SER 195`		`GLY 193;SER 195`
1a5iA01								`SER 195`		`GLY 193;SER 195`
1bdaA01								`SER 195`		`GLY 193;SER 195`
1bdaB01								`SER 195`		`GLY 193;SER 195`
1rtfB01								`SER 195`		`GLY 193;SER 195`
1a5hA02								`HIS 57;ASP 102`
1a5hB02								`HIS 57;ASP 102`
1a5iA02								`HIS 57;ASP 102`
1bdaA02								`HIS 57;ASP 102`
1bdaB02								`HIS 57;ASP 102`
1rtfB02								`HIS 57;ASP 102`

references
[1]
PubMed ID	6685059
Journal	FEBS Lett
Year	1983
Volume	163
Pages	37-41
Authors	Banyai L, Varadi A, Patthy L
Title	Common evolutionary origin of the fibrin-binding structures of fibronectin and tissue-type plasminogen activator.
[2]
PubMed ID	3030730
Journal	EMBO J
Year	1986
Volume	5
Pages	3525-30
Authors	Verheijen JH, Caspers MP, Chang GT, de Munk GA, Pouwels PH, Enger-Valk BE
Title	Involvement of finger domain and kringle 2 domain of tissue-type plasminogen activator in fibrin binding and stimulation of activity by fibrin.
[3]
PubMed ID	3021732
Journal	J Biol Chem
Year	1986
Volume	261
Pages	14214-8
Authors	van Zonneveld AJ, Veerman H, Pannekoek H
Title	On the interaction of the finger and the kringle-2 domain of tissue-type plasminogen activator with fibrin. Inhibition of kringle-2 binding to fibrin by epsilon-amino caproic acid.
[4]
PubMed ID	3088564
Journal	Proc Natl Acad Sci U S A
Year	1986
Volume	83
Pages	4670-4
Authors	van Zonneveld AJ, Veerman H, Pannekoek H
Title	Autonomous functions of structural domains on human tissue-type plasminogen activator.
[5]
PubMed ID	2846282
Journal	EMBO J
Year	1988
Volume	7
Pages	2731-40
Authors	Gething MJ, Adler B, Boose JA, Gerard RD, Madison EL, McGookey D, Meidell RS, Roman LM, Sambrook J
Title	Variants of human tissue-type plasminogen activator that lack specific structural domains of the heavy chain.
[6]
Comments	STRUCTURE BY NMR OF KRINGLE 2.
Medline ID	90122799
PubMed ID	2558718
Journal	Biochemistry
Year	1989
Volume	28
Pages	9350-60
Authors	Byeon IJ, Kelley RF, Llinas M
Title	1H NMR structural characterization of a recombinant kringle 2 domain from human tissue-type plasminogen activator.
Related UniProtKB	P00750
[7]
PubMed ID	2497771
Journal	Biochemistry
Year	1989
Volume	28
Pages	1884-91
Authors	Cleary S, Mulkerrin MG, Kelley RF
Title	Purification and characterization of tissue plasminogen activator kringle-2 domain expressed in Escherichia coli.
[8]
PubMed ID	2502177
Journal	Biochemistry
Year	1989
Volume	28
Pages	4047-54
Authors	Kelley RF, Cleary S
Title	Effect of residue 65 substitutions on thermal stability of tissue plasminogen activator kringle-2 domain.
[9]
PubMed ID	2477307
Journal	Gene
Year	1989
Volume	79
Pages	333-44
Authors	Stern A, Mattes R, Buckel P, Weidle UH
Title	Functional topology of human tissue-type plasminogen activator: characterization of two deletion derivatives and of a duplication derivative.
[10]
PubMed ID	2556697
Journal	Protein Eng
Year	1989
Volume	3
Pages	111-6
Authors	Markland W, Pollock D, Livingston DJ
Title	Tissue-type plasminogen activator variants with domain duplications and rearrangements.
[11]
PubMed ID	2108143
Journal	J Biol Chem
Year	1990
Volume	265
Pages	5540-5
Authors	Ahern TJ, Morris GE, Barone KM, Horgan PG, Timony GA, Angus LB, Henson KS, Stoudemire JB, Langer-Safer PR, Larsen GR
Title	Site-directed mutagenesis in human tissue-plasminogen activator. Distinguishing sites in the amino-terminal region required for full fibrinolytic activity and rapid clearance from the circulation.
[12]
PubMed ID	2108167
Journal	J Biol Chem
Year	1990
Volume	265
Pages	5170-7
Authors	Burck PJ, Berg DH, Warrick MW, Berg DT, Walls JD, Jaskunas SR, Crisel RM, Weigel B, Vlahos CJ, McClure DB, et al
Title	Characterization of a modified human tissue plasminogen activator comprising a kringle-2 and a protease domain.
[13]
PubMed ID	2115513
Journal	J Biol Chem
Year	1990
Volume	265
Pages	12184-91
Authors	Collen D, Lijnen HR, Bulens F, Vandamme AM, Tulinsky A, Nelles L
Title	Biochemical and functional characterization of human tissue-type plasminogen activator variants with mutagenized kringle domains.
[14]
PubMed ID	2117612
Journal	J Biol Chem
Year	1990
Volume	265
Pages	14606-11
Authors	Wilhelm OG, Jaskunas SR, Vlahos CJ, Bang NU
Title	Functional properties of the recombinant kringle-2 domain of tissue plasminogen activator produced in Escherichia coli.
[15]
Comments	STRUCTURE BY NMR OF KRINGLE 2.
Medline ID	91200042
PubMed ID	1901789
Journal	Eur J Biochem
Year	1991
Volume	197
Pages	155-65
Authors	Byeon IJ, Kelley RF, Llinas M
Title	Kringle-2 domain of the tissue-type plasminogen activator. 1H-NMR assignments and secondary structure.
Related UniProtKB	P00750
[16]
PubMed ID	1900516
Journal	J Biol Chem
Year	1991
Volume	266
Pages	5191-201
Authors	Bennett WF, Paoni NF, Keyt BA, Botstein D, Jones AJ, Presta L, Wurm FM, Zoller MJ
Title	High resolution analysis of functional determinants on human tissue-type plasminogen activator.
[17]
Comments	DISULFIDE BONDS IN KRINGLE 2.
Medline ID	91244765
PubMed ID	1645336
Journal	J Biol Chem
Year	1991
Volume	266
Pages	10070-2
Authors	Vlahos CJ, Wilhelm OG, Hassell T, Jaskunas SR, Bang NU
Title	Disulfide pairing of the recombinant kringle-2 domain of tissue plasminogen activator produced in Escherichia coli.
Related UniProtKB	P00750
[18]
Comments	STRUCTURE BY NMR OF KRINGLE 2.
Medline ID	92106329
PubMed ID	1762144
Journal	J Mol Biol
Year	1991
Volume	222
Pages	1035-51
Authors	Byeon IJ, Llinas M
Title	Solution structure of the tissue-type plasminogen activator kringle 2 domain complexed to 6-aminohexanoic acid an antifibrinolytic drug.
Related PDB	1pk2
Related UniProtKB	P00750
[19]
PubMed ID	1309292
Journal	Arch Biochem Biophys
Year	1992
Volume	292
Pages	206-12
Authors	De Serrano VS, Sehl LC, Castellino FJ
Title	Direct identification of lysine-33 as the principal cationic center of the omega-amino acid binding site of the recombinant kringle 2 domain of tissue-type plasminogen activator.
[20]
PubMed ID	1554717
Journal	Biochemistry
Year	1992
Volume	31
Pages	3326-35
Authors	De Serrano VS, Castellino FJ
Title	Role of tryptophan-74 of the recombinant kringle 2 domain of tissue-type plasminogen activator in its omega-amino acid binding properties.
[21]
Comments	X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF KRINGLE 2.
Medline ID	92118803
PubMed ID	1310033
Journal	Biochemistry
Year	1992
Volume	31
Pages	270-9
Authors	de Vos AM, Ultsch MH, Kelley RF, Padmanabhan K, Tulinsky A, Westbrook ML, Kossiakoff AA
Title	Crystal structure of the kringle 2 domain of tissue plasminogen activator at 2.4-A resolution.
Related PDB	1tpk
Related UniProtKB	P00750
[22]
PubMed ID	1731899
Journal	Biochemistry
Year	1992
Volume	31
Pages	419-22
Authors	Eastman D, Wurm FM, van Reis R, Higgins DL
Title	A region of tissue plasminogen activator that affects plasminogen activation differentially with various fibrin(ogen)-related stimulators.
[23]
PubMed ID	1315765
Journal	J Biol Chem
Year	1992
Volume	267
Pages	9668-77
Authors	Bassel-Duby R, Jiang NY, Bittick T, Madison E, McGookey D, Orth K, Shohet R, Sambrook J, Gething MJ
Title	Tyrosine 67 in the epidermal growth factor-like domain of tissue-type plasminogen activator is important for clearance by a specific hepatic receptor.
[24]
Comments	STRUCTURE BY NMR OF 38-85.
Medline ID	92292163
PubMed ID	1602484
Journal	J Mol Biol
Year	1992
Volume	225
Pages	821-33
Authors	Downing AK, Driscoll PC, Harvey TS, Dudgeon TJ, Smith BO, Baron M, Campbell ID
Title	Solution structure of the fibrin binding finger domain of tissue-type plasminogen activator determined by 1H nuclear magnetic resonance.
Related PDB	1tpm,1tpn
Related UniProtKB	P00750
[25]
PubMed ID	1321420
Journal	Protein Eng
Year	1992
Volume	5
Pages	93-100
Authors	Kohnert U, Rudolph R, Verheijen JH, Weening-Verhoeff EJ, Stern A, Opitz U, Martin U, Lill H, Prinz H, Lechner M, et al
Title	Biochemical properties of the kringle 2 and protease domains are maintained in the refolded t-PA deletion variant BM 06.022.
[26]
PubMed ID	1287881
Journal	Thromb Haemost
Year	1992
Volume	68
Pages	672-7
Authors	Yahara H, Matsumoto K, Maruyama H, Nagaoka T, Ikenaka Y, Yajima K, Fukao H, Ueshima S, Matsuo O
Title	Recombinant variants of tissue-type plasminogen activator containing amino acid substitutions in the finger domain.
[27]
PubMed ID	8424682
Journal	Arch Biochem Biophys
Year	1993
Volume	300
Pages	472-82
Authors	Rydzewski A, Castellino FJ
Title	The effector roles of kringle 1 and kringle 2 in the enzymatic properties of recombinant tissue-type plasminogen activator as revealed by generation of recombinant molecules containing each kringle linked to the protease domain.
[28]
PubMed ID	8385482
Journal	Biochemistry
Year	1993
Volume	32
Pages	3540-8
Authors	De Serrano VS, Castellino FJ
Title	Specific anionic residues of the recombinant kringle 2 domain of tissue-type plasminogen activator that are responsible for stabilization of its interaction with omega-amino acid ligands.
[29]
PubMed ID	8449917
Journal	J Biol Chem
Year	1993
Volume	268
Pages	5550-6
Authors	Lubin IM, Caban R, Runge MS
Title	The tissue plasminogen activator finger domain confers fibrin-dependent enhancement of catalytic activity to single-chain urokinase-type plasminogen activator.
[30]
PubMed ID	8030371
Journal	Acta Biochim Pol
Year	1994
Volume	41
Pages	25-34
Authors	Pietrucha T, Stec WJ, Okruszek A, Uznanski B, Koziolkiewicz M, Wilk A, Plucienniczak A, Swiatkowska M, Cierniewski CS
Title	The epidermal growth factor-like domain from tissue plasminogen activator. Cloning in E. coli, purification and ESR studies of its interaction with human blood platelets.
[31]
PubMed ID	8142348
Journal	Biochemistry
Year	1994
Volume	33
Pages	3509-14
Authors	De Serrano VS, Castellino FJ
Title	Involvement of tyrosine-76 of the kringle 2 domain of tissue-type plasminogen activator in its thermal stability and its omega-amino acid ligand binding site.
[32]
PubMed ID	8312251
Journal	Biochemistry
Year	1994
Volume	33
Pages	1340-4
Authors	De Serrano VS, Castellino FJ
Title	Role of the strictly conserved tryptophan-25 residue in the stabilization of the structure and in the ligand binding properties of the kringle 2 domain of tissue-type plasminogen activator.
[33]
PubMed ID	8175674
Journal	J Biol Chem
Year	1994
Volume	269
Pages	12639-44
Authors	Horrevoets AJ, Smilde A, de Vries C, Pannekoek H
Title	The specific roles of finger and kringle 2 domains of tissue-type plasminogen activator during in vitro fibrinolysis.
[34]
Comments	X-ray crystallography
PubMed ID	8069221
Journal	Protein Sci
Year	1994
Volume	3
Pages	898-910
Authors	Padmanabhan K, Wu TP, Ravichandran KG, Tulinsky A
Title	Kringle-kringle interactions in multimer kringle structures.
Related PDB	1pmk,1pml
[35]
PubMed ID	7740461
Journal	Thromb Haemost
Year	1994
Volume	72
Pages	900-5
Authors	Stringer HA, van Swieten P, Horrevoets AJ, Smilde A, Pannekoek H
Title	The role of the finger domain of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) in initiation and progression of thrombolysis.
[36]
PubMed ID	7893685
Journal	Biochemistry
Year	1995
Volume	34
Pages	2739-50
Authors	Byeon IJ, Kelley RF, Mulkerrin MG, An SS, Llinas M
Title	Ligand binding to the tissue-type plasminogen activator kringle 2 domain: structural characterization by 1H-NMR.
[37]
PubMed ID	7711052
Journal	Biochim Biophys Acta
Year	1995
Volume	1248
Pages	1-10
Authors	Rudd PM, Woods RJ, Wormald MR, Opdenakker G, Downing AK, Campbell ID, Dwek RA
Title	The effects of variable glycosylation on the functional activities of ribonuclease, plasminogen and tissue plasminogen activator.
[38]
PubMed ID	8530479
Journal	J Biol Chem
Year	1995
Volume	270
Pages	30486-90
Authors	Smith JW, Tachias K, Madison EL
Title	Protein loop grafting to construct a variant of tissue-type plasminogen activator that binds platelet integrin alpha IIb beta 3.
[39]
PubMed ID	7479691
Journal	Protein Eng
Year	1995
Volume	8
Pages	293-300
Authors	Bakker AH, Rehberg EF, Marotti KR, Verheijen JH
Title	The position of the structurally autonomous kringle 2 domain influences the functional features of tissue-type plasminogen activator.
[40]
Comments	STRUCTURE BY NMR OF 36-126.
Medline ID	96027104
PubMed ID	7582899
Journal	Structure
Year	1995
Volume	3
Pages	823-33
Authors	Smith BO, Downing AK, Driscoll PC, Dudgeon TJ, Campbell ID
Title	The solution structure and backbone dynamics of the fibronectin type I and epidermal growth factor-like pair of modules of tissue-type plasminogen activator.
Related PDB	1tpg
Related UniProtKB	P00750
[41]
PubMed ID	8605163
Journal	Biochemistry
Year	1996
Volume	35
Pages	3270-6
Authors	Hu CK, Kohnert U, Sturzebecher J, Fischer S, Llinas M
Title	Complexation of the tissue plasminogen activator protease with benzamidine-type inhibitors: interference by the kringle 2 module.
[42]
Comments	X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF CATALYTIC DOMAIN.
Medline ID	96200985
PubMed ID	8613982
Journal	J Mol Biol
Year	1996
Volume	258
Pages	117-35
Authors	Lamba D, Bauer M, Huber R, Fischer S, Rudolph R, Kohnert U, Bode W
Title	The 2.3 A crystal structure of the catalytic domain of recombinant two-chain human tissue-type plasminogen activator.
Related PDB	1rtf
Related UniProtKB	P00750
[43]
PubMed ID	8736495
Journal	Protein Eng
Year	1996
Volume	9
Pages	283-90
Authors	Sehl LC, Nguyen HV, Berleau LT, Arcila P, Bennett WF, Keyt BA
Title	Locating the unpaired cysteine of tissue-type plasminogen activator.
[44]
PubMed ID	9201906
Journal	Biochemistry
Year	1997
Volume	36
Pages	7652-63
Authors	Chang Y, Zajicek J, Castellino FJ
Title	Role of tryptophan-63 of the kringle 2 domain of tissue-type plasminogen activator in its thermal stability, folding, and ligand binding properties.
[45]
Comments	TISSUE=Salivary gland;
Medline ID	98022741
PubMed ID	9354616
Journal	Biochemistry
Year	1997
Volume	36
Pages	13483-93
Authors	Renatus M, Stubbs MT, Huber R, Bringmann P, Donner P, Schleuning WD, Bode W
Title	Catalytic domain structure of vampire bat plasminogen activator: a molecular paradigm for proteolysis without activation cleavage.
Related PDB	1a5i
Related UniProtKB	P98119
[46]
PubMed ID	9434908
Journal	Curr Opin Struct Biol
Year	1997
Volume	7
Pages	865-72
Authors	Bode W, Renatus M
Title	Tissue-type plasminogen activator: variants and crystal/solution structures demarcate structural determinants of function.
[47]
Comments	X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF CATALYTIC DOMAIN.
Medline ID	97449126
PubMed ID	9305622
Journal	EMBO J
Year	1997
Volume	16
Pages	4797-805
Authors	Renatus M, Engh RA, Stubbs MT, Huber R, Fischer S, Kohnert U, Bode W
Title	Lysine 156 promotes the anomalous proenzyme activity of tPA: X-ray crystal structure of single-chain human tPA.
Related PDB	1bda
Related UniProtKB	P00750
[48]
Comments	X-ray crystallography
PubMed ID	9268299
Journal	J Biol Chem
Year	1997
Volume	272
Pages	21713-9
Authors	Renatus M, Bode W, Huber R, Sturzebecher J, Prasa D, Fischer S, Kohnert U, Stubbs MT
Title	Structural mapping of the active site specificity determinants of human tissue-type plasminogen activator. Implications for the design of low molecular weight substrates and inhibitors.
Related PDB	1a5h
[49]
PubMed ID	10543954
Journal	J Mol Biol
Year	1999
Volume	293
Pages	613-27
Authors	Dekker RJ, Eichinger A, Stoop AA, Bode W, Pannekoek H, Horrevoets AJ
Title	The variable region-1 from tissue-type plasminogen activator confers specificity for plasminogen activator inhibitor-1 to thrombin by facilitating catalysis: release of a kinetic block by a heterologous protein surface loop.
[50]
PubMed ID	10408340
Journal	J Pept Res
Year	1999
Volume	53
Pages	656-64
Authors	Chang Y, Nilsen SL, Castellino FJ
Title	Functional and structural consequences of aromatic residue substitutions within the kringle-2 domain of tissue-type plasminogen activator.
[51]
PubMed ID	10744692
Journal	J Biol Chem
Year	2000
Volume	275
Pages	10112-20
Authors	Stewart RJ, Fredenburgh JC, Leslie BA, Keyt BA, Rischke JA, Weitz JI
Title	Identification of the mechanism responsible for the increased fibrin specificity of TNK-tissue plasminogen activator relative to tissue plasminogen activator.
[52]
PubMed ID	12696753
Journal	Curr Top Dev Biol
Year	2003
Volume	54
Pages	263-312
Authors	Ellis V
Title	Plasminogen activation at the cell surface.
[53]
PubMed ID	14500731
Journal	J Biol Chem
Year	2003
Volume	278
Pages	48197-203
Authors	Perron MJ, Blouse GE, Shore JD
Title	Distortion of the catalytic domain of tissue-type plasminogen activator by plasminogen activator inhibitor-1 coincides with the formation of stable serpin-proteinase complexes.

comments

This enzyme belongs to the peptidase family-S1.
This enzyme is composed of six domains; fibronectin type-I domain, EGF-like domain, Kringle1 domain, Kringle2 domain and catalytic domains of serine protease.
The PDB structures correspond to the following domains.
(PDB;1tpg, Swiss-prot;P00750, residues 36-126 [EGF-like/Kringle1 domain],
PDB;1pk2, Swiss-prot;P00750, residues 209-297 [klingle2 domain],
PDB;1a5hA, Swiss-prot;P00750, residues 311-562 [Catalytic domain]).
As this enzyme has got a classical catalytic triad composed of Ser/His/Asp, which is the same as that of trypsin (D00197 in EzCatDB), it should have a similar mechanism.

created	updated
2004-08-13	2011-02-21

Copyright: Nozomi Nagano, JST & CBRC-AIST
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