1rtf: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1rtf.jpg|left|200px]] | [[Image:1rtf.jpg|left|200px]] | ||
<!-- | |||
The line below this paragraph, containing "STRUCTURE_1rtf", creates the "Structure Box" on the page. | |||
You may change the PDB parameter (which sets the PDB file loaded into the applet) | |||
or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |||
or leave the SCENE parameter empty for the default display. | |||
| | --> | ||
| | {{STRUCTURE_1rtf| PDB=1rtf | SCENE= }} | ||
}} | |||
'''COMPLEX OF BENZAMIDINE WITH THE CATALYTIC DOMAIN OF HUMAN TWO CHAIN TISSUE PLASMINOGEN ACTIVATOR [(TC)-T-PA]''' | '''COMPLEX OF BENZAMIDINE WITH THE CATALYTIC DOMAIN OF HUMAN TWO CHAIN TISSUE PLASMINOGEN ACTIVATOR [(TC)-T-PA]''' | ||
| Line 28: | Line 25: | ||
[[Category: Bode, W.]] | [[Category: Bode, W.]] | ||
[[Category: Lamba, D.]] | [[Category: Lamba, D.]] | ||
[[Category: | [[Category: Fibrinolytic enzyme]] | ||
[[Category: | [[Category: Serine protease]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 07:53:05 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 07:53, 3 May 2008
COMPLEX OF BENZAMIDINE WITH THE CATALYTIC DOMAIN OF HUMAN TWO CHAIN TISSUE PLASMINOGEN ACTIVATOR [(TC)-T-PA]
OverviewOverview
Tissue-type plasminogen activator (t-PA), a multidomainal serine proteinase of the trypsin-family, catalyses the rate-limiting step in fibrinolysis, the activation of plasminogen to the fibrin-degrading proteinase plasmin. Trigonal crystals have been obtained of the recombinant catalytic domain of human-two-chain t-PA, consisting of a 17 residue A chain and the 252 residue B chain. Its X-ray crystal structure has been solved applying Patterson and isomorphous replacement methods, and has been crystallographically refined to an R-value of 0.184 at 2.3 A resolution. The chain fold, active-site geometry and Ile276-Asp477 salt bridge are similar to that observed for trypsin. A few surface-located insertion loops differ significantly, however. The disulfide bridge Cys315-Cys384, practically unique to the plasminogen activators, is incorporated without drastic conformational changes as the insertion loop preceding Cys384 makes a bulge on the molecular surface. The unique basic insertion loop Lys296-Arg304 flanking the primed subsites, which has been shown to be of importance for PAI-1 binding and for fibrin specificity, is partially disordered; it can therefore freely adapt to proteins docking to the active site. The S1 pocket of t-PA is almost identical to that of trypsin, whereas the S2 site is considerably reduced in size by the imposing Tyr368 side-chain, in agreement with the measured preference for P1 Arg and P2 Gly residues. The neighbouring S3-S4 hydrophobic groove is mainly hydrophobic in nature. The structure of the proteinase domain of two-chain t-PA suggests that the formation of a salt bridge between Lys429 and Asp477 may contribute to the unusually high catalytic activity of single-chain t-PA, thus stabilizing the catalytically active conformation without unmasking the Ile276 amino terminus. Modeling studies show that the covalently bound kringle 2 domain in full-length t-PA could interact with an extended hydrophobic groove in the catalytic domain; in such a docking geometry its "lysine binding site" and the "fibrin binding patch" of the catalytic domain are in close proximity.
About this StructureAbout this Structure
1RTF is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
The 2.3 A crystal structure of the catalytic domain of recombinant two-chain human tissue-type plasminogen activator., Lamba D, Bauer M, Huber R, Fischer S, Rudolph R, Kohnert U, Bode W, J Mol Biol. 1996 Apr 26;258(1):117-35. PMID:8613982 Page seeded by OCA on Sat May 3 07:53:05 2008