Biomaterial Database

Mechanism of activation of coagulation factor XI by factor XIIa studied with monoclonal antibodies. 1986

H Akiyama, and D Sinha, and F S Seaman, and E P Kirby, and P N Walsh

The interaction of Factor XIIa with Factor XI was investigated using two monoclonal antibodies, one (3Cl) directed against the heavy chain of Factor XIa and the other (5F4) against its light chain. 3C1 either as intact IgG or as Fab' fragment, enhanced the rate of Factor XIa generation in the fluid phase but inhibited it in the presence of kaolin and high molecular weight (HMW) kininogen. In contrast, the Fab' fragments of 5F4 inhibited only the fluid phase activation and had no effect on the surface-mediated activation. 3C1 was found to block the binding of Factor XI to HMW kininogen, whereas 5F4 did not. We conclude: a domain on the heavy chain region of Factor XI is essential for binding to HMW kininogen and for optimal surface-mediated activation by Factor XIIa; and binding of 3C1 to Factor XI changes its conformation rendering it a more favorable substrate for Factor XIIa in the fluid phase.

UI	MeSH Term	Description	Entries
D007140	Immunoglobulin Fab Fragments	Univalent antigen-binding fragments composed of one entire IMMUNOGLOBULIN LIGHT CHAIN and the amino terminal end of one of the IMMUNOGLOBULIN HEAVY CHAINS from the hinge region, linked to each other by disulfide bonds. Fab contains the IMMUNOGLOBULIN VARIABLE REGIONS, which are part of the antigen-binding site, and the first IMMUNOGLOBULIN CONSTANT REGIONS. This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.	Fab Fragment,Fab Fragments,Ig Fab Fragments,Immunoglobulins, Fab Fragment,Fab Immunoglobulin Fragments,Immunoglobulin Fab Fragment,Immunoglobulins, Fab,Fab Fragment Immunoglobulins,Fab Fragment, Immunoglobulin,Fab Fragments, Immunoglobulin,Fragment Immunoglobulins, Fab,Fragment, Fab,Immunoglobulin Fragments, Fab
D007616	Kaolin	The most common mineral of a group of hydrated aluminum silicates, approximately H2Al2Si2O8-H2O. It is prepared for pharmaceutical and medicinal purposes by levigating with water to remove sand, etc. (From Merck Index, 11th ed) The name is derived from Kao-ling (Chinese: "high ridge"), the original site. (From Grant & Hackh's Chemical Dictionary, 5th ed)	Kaolinite
D007704	Kininogens	Endogenous peptides present in most body fluids. Certain enzymes convert them to active KININS which are involved in inflammation, blood clotting, complement reactions, etc. Kininogens belong to the cystatin superfamily. They are cysteine proteinase inhibitors. HIGH-MOLECULAR-WEIGHT KININOGEN; (HMWK); is split by plasma kallikrein to produce BRADYKININ. LOW-MOLECULAR-WEIGHT KININOGEN; (LMWK); is split by tissue kallikrein to produce KALLIDIN.	Cystatins, Kininogen,Kininogen,Prekinins,Prokinins,T-Kininogen,Thiostatin,Kininogen Cystatins,T Kininogen
D010446	Peptide Fragments	Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.	Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D005172	Factor XI	Stable blood coagulation factor involved in the intrinsic pathway. The activated form XIa activates factor IX to IXa. Deficiency of factor XI is often called hemophilia C.	Coagulation Factor XI,Plasma Thromboplastin Antecedent,Blood Coagulation Factor XI,Factor 11,Factor Eleven,Antecedent, Plasma Thromboplastin,Factor XI, Coagulation,Thromboplastin Antecedent, Plasma
D005174	Factor XII	Stable blood coagulation factor activated by contact with the subendothelial surface of an injured vessel. Along with prekallikrein, it serves as the contact factor that initiates the intrinsic pathway of blood coagulation. Kallikrein activates factor XII to XIIa. Deficiency of factor XII, also called the Hageman trait, leads to increased incidence of thromboembolic disease. Mutations in the gene for factor XII that appear to increase factor XII amidolytic activity are associated with HEREDITARY ANGIOEDEMA TYPE III.	Coagulation Factor XII,Hageman Factor,Factor 12,Factor Twelve
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000911	Antibodies, Monoclonal	Antibodies produced by a single clone of cells.	Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015956	Factor XIIa	Activated form of factor XII. In the initial event in the intrinsic pathway of blood coagulation, kallikrein (with cofactor HIGH MOLECULAR WEIGHT KININOGEN) cleaves factor XII to XIIa. Factor XIIa is then further cleaved by kallikrein, plasmin, and trypsin to yield smaller factor XII fragments (Hageman-Factor fragments). These fragments increase the activity of prekallikrein to kallikrein but decrease the procoagulant activity of factor XII.	Coagulation Factor XIIa,Factor XII, Activated,Activated Factor XII,Blood Coagulation Factor XII, Activated,Factor 12A,Factor Twelve A,Hageman-Factor Fragments,Prekallikrein Activator,Activator, Prekallikrein,Factor XIIa, Coagulation,Fragments, Hageman-Factor,Hageman Factor Fragments