An X-ray structure of the F1 portion of the mitochondrial ATP synthase shows asymmetry and differences in nucleotide binding of the catalytic β subunits that support the binding change mechanism with an internal rotation of the γ subunit. Other structural and mutational probes of the F1 and F0 portions of the ATP synthase are reviewed, together with kinetic and other evaluations of catalytic site occupancy and behavior during hydrolysis or synthesis of ATP. Subunit function as related to proton translocation and rotational catalysis is considered. Physical demonstrations of the γ subunit rotation have been achieved. The findings have implications for other enzymatic catalyses.

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The ATP Synthase—A Splendid Molecular Machine

Plasminogen activator inhibitors.

The serpin superfamily of proteinase inhibitors: structure, function, and regulation.

PLASMINOGEN ACTIVATOR INHIBITORS 104 Plasminogen Activator Inhibitor 1 104 Plasminogen Activator Inhibitor 2 106 Protease Nexin I .... .... 108 PHYSIOLOGICAL FUNCTIONS OF PLASMINOGEN ACTIVATION ........ 109 Matrix Breakdown 109 Cell Migration 111 Ovulation 113 CONCLUDING REMARKS 115

Cell-associated plasminogen activation: regulation and physiological functions.

Sepsis is a state of disrupted inflammatory homeostasis that is often initiated by infection. The development and progression of sepsis is multi-factorial, and affects the cardiovascular, immunological and endocrine systems of the body. The complexity of sepsis makes the clinical study of sepsis and sepsis therapeutics difficult. Animal models have been developed in an effort to create reproducible systems for studying sepsis pathogenesis and preliminary testing of potential therapeutic agents. However, demonstrated benefit from a therapeutic agent in animal models has rarely been translated into success in human clinical trials. This review summarizes the common animal sepsis models and highlights how results of recent human clinical trials might affect their use.

Animal Models of sepsis: setting the stage

Endothelial cells produce a latent inhibitor of plasminogen activators that can be activated by denaturants.

Mechanism of protein C-dependent clot lysis: role of plasminogen activator inhibitor

Monospecific antiserum to an unusually stable Mr 50,000 plasminogen-activator inhibitor (PAI) purified from cultured bovine aortic endothelial cells was employed in conjunction with reverse fibrin autography to determine whether human platelets, serum, and plasma contain immunologically related inhibitors. Reverse fibrin autography revealed the presence of a Mr 50,000 inhibitor in the platelet and serum samples but not in normal plasma. However, a Mr 50,000 inhibitor was detected in plasma obtained from individuals with increased PAI activity. In each case, treatment of the sample with the anti-inhibitor serum removed the Mr 50,000 inhibitor. The inhibitor present in each sample neutralized exogenously added tissue-type plasminogen activator in a rapid manner. Inhibition was associated with the formation of a NaDodSO4-resistant enzyme-inhibitor complex of Mr 120,000. Again, treatment of the samples with the anti-inhibitor serum removed both the inhibitory activity and the component in these samples that binds to tissue-type plasminogen activator. Thus, the rapidly acting PAI present in human platelets, serum, and patient plasma is immunologically related to the PAI synthesized by cultured bovine aortic endothelial cells. This molecule may be the physiologically relevant inhibitor of plasminogen activator in the vascular system and, as such, may serve an important role in regulating the initiation of vascular fibrinolysis.

https://www.pnas.org/content/pnas/82/24/8710.full.pdf

Carla M. Hekman

Papers

Endothelial cells produce a latent inhibitor of plasminogen activators that can be activated by denaturants.

Mechanism of protein C-dependent clot lysis: role of plasminogen activator inhibitor

The primary plasminogen-activator inhibitors in endothelial cells, platelets, serum, and plasma are immunologically related

Kinetic analysis of the interactions between plasminogen activator inhibitor 1 and both urokinase and tissue plasminogen activator

Fibrinolytic pathways and the endothelium.