Coagulation factor XIII variants with altered thrombin activation rates. 2009

Mette Dahl Andersen, and Marianne Kjalke, and Susanne Bang, and Inger Lautrup-Larsen, and Peter Becker, and Asser Sloth Andersen, and Ole Hvilsted Olsen, and Henning R Stennicke
Biopharmaceutical Research Unit, Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Måløv, Denmark.

Coagulation factor XIII (FXIII) is activated by thrombin and catalyses crosslinking between fibrin monomers thereby providing mechanical strength to the fibrin network. V34L is a common FXIII-A polymorphism found in the activation peptide. FXIII-A V34L is activated faster by thrombin and provides formation of a tighter clot at fibrinogen concentrations in the low end of the physiological range. FXIII-A variants with potentially increased activation rates were generated. Introduction of an optimal thrombin cleavage site, V34L+V35T, increased the activation rate 7.6-fold and facilitated the formation of a fibrin network more resistant to fibrinolysis than obtained with wt FXIII-A. In contrast, introduction of fragments of fibrinopeptide A into the activation peptide resulted in severely impaired activation rates.

UI MeSH Term Description Entries
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D005176 Factor XIII A fibrin-stabilizing plasma enzyme (TRANSGLUTAMINASES) that is activated by THROMBIN and CALCIUM to form FACTOR XIIIA. It is important for stabilizing the formation of the fibrin polymer (clot) which culminates the coagulation cascade. Coagulation Factor XIII,Factor XIII Transamidase,Fibrin Stabilizing Factor,Fibrinase,Laki-Lorand Factor,Blood Coagulation Factor XIII,Factor 13,Factor Thirteen,Laki Lorand Factor,Factor XIII, Coagulation,Stabilizing Factor, Fibrin,Transamidase, Factor XIII,XIII, Coagulation Factor
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D013917 Thrombin An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN. Thrombase,Thrombin JMI,Thrombin-JMI,Thrombinar,Thrombostat,alpha-Thrombin,beta,gamma-Thrombin,beta-Thrombin,gamma-Thrombin,JMI, Thrombin
D017398 Alternative Splicing A process whereby multiple RNA transcripts are generated from a single gene. Alternative splicing involves the splicing together of other possible sets of EXONS during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form a mature RNA. The alternative forms of mature MESSENGER RNA produce PROTEIN ISOFORMS in which one part of the isoforms is common while the other parts are different. RNA Splicing, Alternative,Splicing, Alternative,Alternate Splicing,Nested Transcripts,Alternate Splicings,Alternative RNA Splicing,Alternative RNA Splicings,Alternative Splicings,Nested Transcript,RNA Splicings, Alternative,Splicing, Alternate,Splicing, Alternative RNA,Splicings, Alternate,Splicings, Alternative,Splicings, Alternative RNA,Transcript, Nested,Transcripts, Nested
D020836 Protein Structure, Quaternary The characteristic 3-dimensional shape and arrangement of multimeric proteins (aggregates of more than one polypeptide chain). Quaternary Protein Structure,Protein Structures, Quaternary,Quaternary Protein Structures

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