1BDA

CATALYTIC DOMAIN OF HUMAN SINGLE CHAIN TISSUE PLASMINOGEN ACTIVATOR IN COMPLEX WITH DANSYL-EGR-CMK (DANSYL-GLU-GLY-ARG CHLOROMETHYL KETONE)

1BDA の概要

• エントリーDOI: 10.2210/pdb1bda/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000413
• 分子名称: SINGLE CHAIN TISSUE TYPE PLASMINOGEN ACTIVATOR, N-{[5-(dimethylamino)naphthalen-2-yl]sulfonyl}-L-alpha-glutamyl-N-[(1S)-4-{[amino(iminio)methyl]amino}-1-(chloroacetyl) butyl]glycinamide (3 entities in total)
• 機能のキーワード: trypsin like serine protease, fibrinolytic enzymes, plasminogen activators, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted, extracellular space: P00750
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 60705.57

構造登録者

Bode, W.,Renatus, M.,Engh, R.A. (登録日: 1998-05-07, 公開日: 1999-05-11, 最終更新日: 2024-10-16)

主引用文献

Renatus, M.,Engh, R.A.,Stubbs, M.T.,Huber, R.,Fischer, S.,Kohnert, U.,Bode, W.
Lysine 156 promotes the anomalous proenzyme activity of tPA: X-ray crystal structure of single-chain human tPA.
EMBO J., 16:4797-4805, 1997

PubMed Abstract: 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.

PubMed: 9305622
DOI: 10.1093/emboj/16.16.4797

実験手法

X-RAY DIFFRACTION (3.35 Å)