1bda
From Proteopedia
CATALYTIC DOMAIN OF HUMAN SINGLE CHAIN TISSUE PLASMINOGEN ACTIVATOR IN COMPLEX WITH DANSYL-EGR-CMK (DANSYL-GLU-GLY-ARG CHLOROMETHYL KETONE)
Overview
Tissue type plasminogen activator (tPA) is the physiological initiator of fibrinolysis, activating plasminogen via highly specific proteolysis; plasmin then degrades fibrin with relatively broad specificity. Unlike other chymotrypsin family serine proteinases, tPA is proteolytically active in a single-chain form. This form is also preferred for therapeutic administration of tPA in cases of acute myocardial infarction. The proteolytic cleavage which activates most other chymotrypsin family serine proteinases increases the catalytic efficiency of tPA only 5- to 10-fold. The X-ray crystal structure of the catalytic domain of recombinant human single-chain tPA shows that Lys156 forms a salt bridge with Asp194, promoting an active conformation in the single-chain form. Comparisons with the structures of other serine proteinases that also possess Lys156, such as trypsin, factor Xa and human urokinase plasminogen activator (uPA), identify a set of secondary interactions which are required for Lys156 to fulfil this activating role. These findings help explain the anomalous single-chain activity of tPA and may suggest strategies for design of new therapeutic plasminogen activators.
About this Structure
1BDA is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Lysine 156 promotes the anomalous proenzyme activity of tPA: X-ray crystal structure of single-chain human tPA., Renatus M, Engh RA, Stubbs MT, Huber R, Fischer S, Kohnert U, Bode W, EMBO J. 1997 Aug 15;16(16):4797-805. PMID:9305622 Page seeded by OCA on Fri May 2 11:21:56 2008
