This is an F2 lobe domain consisting of an acyl-CoA binding protein fold found in FERM region of Jak-family tyrosine kinases []. Multidomain JAK molecules interact with receptors through their FERM and SH2-like domains, triggering a series of phosphorylation events, resulting in the activation of their kinase domains []. Overall, the FERM region maintains the typical three-lobed architecture, with an F1 lobe consisting of a ubiquitin-like fold, an F2 lobe consisting of an acyl-CoA binding protein fold, and an F3 lobe consisting of a pleckstrin-homology (PH) fold. JAK1 FERM-F2 domain has been shown to act as the interaction site for the IFNLR1 box1 motif (PxxLxF) of class II cytokine receptors which is essential for kinase activation [].
The fusion glycoproteins from this family are found in ssRNA negative-strand viruses.This protein directs fusion of viral and cellular membranes, resulting in viral penetration,and can direct fusion of infected cells with adjoining cells, resulting in the formation ofsyncytia. The mature form is a dimer of polypeptides F1 and F2 linked by a disulphidebond [].
This is an F1 lobe domain consisting of a ubiquitin like fold found in FERM region of Jak-family tyrosine kinases []. Multidomain JAK molecules interact with receptors through their FERM and SH2-like domains, triggering a series of phosphorylation events, resulting in the activation of their kinase domains []. Overall, the FERM region maintains the typical three-lobed architecture, with an F1 lobe consisting of a ubiquitin-like fold, an F2 lobe consisting of an acyl-CoA binding protein fold, and an F3 lobe consisting of a pleckstrin-homology (PH) fold [].
Alpha2-antiplasmin (alpha2AP; plasmin inhibitor; MEROPS identifier I04.023) is the primary inhibitor of plasmin, a proteinase that digests fibrin, the main component of blood clots. Alpha2-antiplasmin forms an inactive 1:1 stoichiometric complex with plasmin. It also rapidly crosslinks to fibrin during blood clotting by activated coagulation factor XIII, and as a consequence fibrin becomes more resistant to fibrinolysis. Therefore alpha2AP is important in modulating the effectiveness and persistence of fibrin with respect to its susceptibility to digestion and removal by plasmin [, ]. Alpha2-antiplasmin corresponds to clade F2 of the serpin superfamily (MEROPS family I4) [, ].
Aromatic polyketides are assembled by a type II (iterative) polyketide synthases (PKSs) in bacteria. Type II PKS complexes consist of several monofunctional or bifunctional proteins which produce polyketide chains of variable but defined length from a specific starter unit and a number of extender units. They also specify the initial regiospecific folding and cyclization pattern of nascent polyketides either through the action of a cyclase (CYC) subunit or through the combined action of site-specific ketoreductase and CYC subunits [, ]. This family represents a number of cyclases involved in polyketide synthesis in a number of actinobacterial species.Tetracenomycin F2 cyclase (TcmI) catalyses an aromatic rearrangement in the biosynthetic pathaway of tetracenomycin C from Streptomyces glaucescens. The protein is a homodimer where each subunit forms a beta-α-β fold belonging to the ferrodoxin fold superfamily []. Four strands of antiparallel sheets and a layer of alpha helices create a cavity which was proposed to be the active site. This structure shows strong topological similarity to a polyketide monoxygenase () from S. coelicolor which functions in the actinorhodin biosynthesic pathway []. It was suggested, therefore, that this fold is well suited to serve as a framework for rearrangements and chemical modification of polyaromatic substrates.
Aromatic polyketides are assembled by a type II (iterative) polyketide synthases (PKSs) in bacteria. Type II PKS complexes consist of several monofunctional or bifunctional proteins which produce polyketide chains of variable but defined length from a specific starter unit and a number of extender units. They also specify the initial regiospecific folding and cyclization pattern of nascent polyketides either through the action of a cyclase (CYC) subunit or through the combined action of site-specific ketoreductase and CYC subunits [, ]. This superfamily represents a number of cyclases involved in polyketide synthesis in a number of actinobacterial species.Tetracenomycin F2 cyclase (TcmI) catalyses an aromatic rearrangement in the biosynthetic pathaway of tetracenomycin C from Streptomyces glaucescens. The protein is a homodimer where each subunit forms a beta-α-β fold belonging to the ferrodoxin fold superfamily []. Four strands of antiparallel sheets and a layer of alpha helices create a cavity which was proposed to be the active site. This structure shows strong topological similarity to a polyketide monoxygenase () from S. coelicolor which functions in the actinorhodin biosynthesic pathway []. It was suggested, therefore, that this fold is well suited to serve as a framework for rearrangements and chemical modification of polyaromatic substrates.
Thrombin belongs to the MEROPS peptidase family S1, subfamily S1A.Prothrombin consists of an N-terminal gamma-carboxyglutamate (GLA) domain, two kringle domains, and the S1A peptidase catalytic domain. The cleavage of prothrombin to thrombin is catalysed by the prothrombinase enzyme complex that consists of serine protease factor Xa, cofactor Va, phospholipids and calcium. Prothromin is cleaved by this enzyme into three fragments: fragment 1 (F1) consits of the GLA domain and the first Kringle domain; fragment 2 (F2) consists of the second Kringle domain; and thrombin (peptidase catalytic domain). F1 facilitates calcium-dependent binding of the proenzyme to phospholipid surfaces. F2 interacts with factor Va, and once it is released from prothrombin, it can bind thrombin to influence its function [].Thrombin is a member of the trypsin family of S1 peptidases. It catalyses the preferential cleavage of arginine-lysine bonds, converting fibrinogen to fibrin, and releasing fibrinopeptides A and B. Thrombin can itself cleave the N-terminal fragment (fragment 1) of prothrombin, prior to its activation by factor Xa. Its effects are mediated by the thrombin receptor. Structures of the thrombin A-chain []and B-chain []have been determined. The most conserved portions of the B chain are the active-site residues and adjacent amino acids, the B loop, and the primary substrate-binding region []. The extent of sequence similarity between species and the conservation of many of the functional/structural motifs suggests that, in addition to their role in blood coagulation, vertebrate thrombins may play an important role in the general mechanisms of wound repair [].
