Sandbox Reserved 1482: Difference between revisions
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Factor VIIIa is obtained by cleavage and release of the B domain <ref name="wikipedia" /><ref name="Ngo" /><ref name="toole">Toole JJ, Pittman DD, Orr EC, Murtha P, Wasley LC & Kaufman RJ. A large region (approximately equal to 95 kDa) of human factor VIII is dispensable for ''in vitro'' procoagulant activity. Proceedings of the National Academy of Sciences. 1986 Aug; 83(16): 5939-5942. PMID: 3016730 doi https://doi.org/10.1073/pnas.83.16.5939</ref>. Although factor VIIIa can be formed from at least two cleavages involving Arg372 and Arg1689, fully factor VIIIa is obtained by a third cleavage at Arg740 <ref name="Ngo" />. | Factor VIIIa is obtained by cleavage and release of the B domain <ref name="wikipedia" /><ref name="Ngo" /><ref name="toole">Toole JJ, Pittman DD, Orr EC, Murtha P, Wasley LC & Kaufman RJ. A large region (approximately equal to 95 kDa) of human factor VIII is dispensable for ''in vitro'' procoagulant activity. Proceedings of the National Academy of Sciences. 1986 Aug; 83(16): 5939-5942. PMID: 3016730 doi https://doi.org/10.1073/pnas.83.16.5939</ref>. Although factor VIIIa can be formed from at least two cleavages involving Arg372 and Arg1689, fully factor VIIIa is obtained by a third cleavage at Arg740 <ref name="Ngo" />. | ||
The two chain that result are a heavy and a light chains <ref name="Ngo" /><ref name="El" /><ref name="pdb" />. | The two chain that result are a heavy and a light chains <ref name="Ngo" /><ref name="El" /><ref name="pdb" />. | ||
The <scene name='80/802656/Heavy_chain/4'>heavy chain</scene> has a various size (90 or 120 kDa) <ref name="wikipedia" /><ref name="Binhoreau">Bihoreau N, Fontaine-Aupart MP, Lehegarat A, Desmadril M, Yon JM. First determination of the secondary structure of purified factor VIII light chain. Biochem J. 1992 Nov; 288 ( Pt 1): 35-40. PMID:1445279 doi: 10.1042/bj2880035</ref>. It consists of the A<sub>1</sub>-A<sub>2</sub> domains <ref name="wikipedia" /><ref name="El" /><ref name="Binhoreau" />. Both A<sub>1</sub> and A<sub>2</sub> domains are built up of two connected β barrels <ref name="Ngo" />. | • The <scene name='80/802656/Heavy_chain/4'>heavy chain</scene> has a various size (90 or 120 kDa) <ref name="wikipedia" /><ref name="Binhoreau">Bihoreau N, Fontaine-Aupart MP, Lehegarat A, Desmadril M, Yon JM. First determination of the secondary structure of purified factor VIII light chain. Biochem J. 1992 Nov; 288 ( Pt 1): 35-40. PMID:1445279 doi: 10.1042/bj2880035</ref>. It consists of the A<sub>1</sub>-A<sub>2</sub> domains <ref name="wikipedia" /><ref name="El" /><ref name="Binhoreau" />. Both A<sub>1</sub> and A<sub>2</sub> domains are built up of two connected β barrels <ref name="Ngo" />. | ||
The <scene name='80/802656/Light_chain/2'>light chain</scene> has a molecular weight of 80 kDa and is composed of 684 amino acids <ref name="Binhoreau" />. It contains two domains: a unique A domain of 371 amino acids and a duplicated C domain of 153 amino acids and 160 amino acids, respectively <ref name="Binhoreau" />. These domains are ranked in the following order A<sub>3</sub>-C<sub>1</sub>-C<sub>2</sub> <ref name="wikipedia" /><ref name="Binhoreau" />. It is composed of 42 % irregular structure, 36 % β-strands, and 22 % α-helices <ref name="Binhoreau" />. The C<sub>1</sub> and C<sub>2</sub> domains are defined by a distorted β barrel, while A<sub>3</sub>, as well as A<sub>1</sub> and A<sub>2</sub>, is composed of two connected β barrels <ref name="Ngo" />. This chain also contains of the major binding site of von Willebrand Factor at its N-terminus <ref name="Binhoreau" />. | • The <scene name='80/802656/Light_chain/2'>light chain</scene> has a molecular weight of 80 kDa and is composed of 684 amino acids <ref name="Binhoreau" />. It contains two domains: a unique A domain of 371 amino acids and a duplicated C domain of 153 amino acids and 160 amino acids, respectively <ref name="Binhoreau" />. These domains are ranked in the following order A<sub>3</sub>-C<sub>1</sub>-C<sub>2</sub> <ref name="wikipedia" /><ref name="Binhoreau" />. It is composed of 42 % irregular structure, 36 % β-strands, and 22 % α-helices <ref name="Binhoreau" />. The C<sub>1</sub> and C<sub>2</sub> domains are defined by a distorted β barrel, while A<sub>3</sub>, as well as A<sub>1</sub> and A<sub>2</sub>, is composed of two connected β barrels <ref name="Ngo" />. This chain also contains of the major binding site of von Willebrand Factor at its N-terminus <ref name="Binhoreau" />. | ||
Both chains are non-covalently associated through to a calcium ion to form the active heterodimer <ref name="Ngo" /><ref name="Binhoreau" />. This complex is the pro-coagulant factor VIIIa <ref name="wikipedia" />. | Both chains are non-covalently associated through to a calcium ion to form the active heterodimer <ref name="Ngo" /><ref name="Binhoreau" />. This complex is the pro-coagulant factor VIIIa <ref name="wikipedia" />. | ||
Such an association is essential for the functioning of the factor VIII <ref name="Binhoreau" />. | Such an association is essential for the functioning of the factor VIII <ref name="Binhoreau" />. | ||
====Ligands==== | ====Ligands==== | ||
