Factor XIa: Difference between revisions
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[[Image:Coag_cartoon.jpg |left| thumb |300px| Schematic representation of the coagulation response]] | [[Image:Coag_cartoon.jpg |left| thumb |300px| Schematic representation of the coagulation response]] | ||
{{Clear}} | {{Clear}} | ||
__TOC__ | |||
==Coagulation Factor XIa== | ==Coagulation Factor XIa== | ||
===Introduction=== | ===Introduction=== | ||
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Amino acid substitutions such as Phe283Leu<ref>PMID:17257616</ref> and Gly350Glu<ref>PMID:15026311 </ref> in the heavy chain results in an increased dimer dissociation and absence of dimer formation respectively. Some mutations in the factor XI A4 domain and catalytic domains are inherited as autosomal recessive bleeding diathesis however, other amino acid substitutions are exert a dominant negative effect on the normal monomer subunit affecting protein secretion. Studies suggest that dimerization is not affected under dominant negative mutations but the mutant subunit traps the normal subunit in the cell preventing its secretion. Majority of these missense mutations:Ser225Phe, Cys398Tyr, Gly400Val and Trp569Ser which produce a dominant negative effect involves residues found in the catalytic domain<ref>PMID:15026311 </ref>. | Amino acid substitutions such as Phe283Leu<ref>PMID:17257616</ref> and Gly350Glu<ref>PMID:15026311 </ref> in the heavy chain results in an increased dimer dissociation and absence of dimer formation respectively. Some mutations in the factor XI A4 domain and catalytic domains are inherited as autosomal recessive bleeding diathesis however, other amino acid substitutions are exert a dominant negative effect on the normal monomer subunit affecting protein secretion. Studies suggest that dimerization is not affected under dominant negative mutations but the mutant subunit traps the normal subunit in the cell preventing its secretion. Majority of these missense mutations:Ser225Phe, Cys398Tyr, Gly400Val and Trp569Ser which produce a dominant negative effect involves residues found in the catalytic domain<ref>PMID:15026311 </ref>. | ||
==3D structures of Factor XIa== | |||
[[Factor XIa 3D structures]] | |||
</StructureSection> | </StructureSection> | ||
==3D structures of Factor XIa== | ==3D structures of Factor XIa== | ||
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**[[3bg8]] – hFXIa + clavatadine<br /> | **[[3bg8]] – hFXIa + clavatadine<br /> | ||
**[[1zpb]], [[2fda]] - hFXIa (mutant) + ketothiazole inhibitor<br /> | **[[1zpb]], [[2fda]] - hFXIa (mutant) + ketothiazole inhibitor<br /> | ||
**[[4na7]], [[4na8]], [[4y8x]], [[ | **[[4na7]], [[4na8]], [[4y8x]], [[5q0d]], [[5q0e]], [[5q0g]], [[5q0h]], [[5qck]], [[5qqp]], [[5qtt]], [[5qtu]], [[5qtv]], [[5qtw]], [[5qtx]], [[5qty]] - hFXIa + inhibitor<br /> | ||
**[[4y8z]], [[6vlu]] - hFXIa + quinoline inhibitor<br /> | **[[4y8z]], [[5qcl]], [[5qcm]], [[5qcn]], [[6vlu]] - hFXIa + quinoline inhibitor<br /> | ||
**[[5e2o]], [[5exm]], [[5tkt]], [[6ts4]], [[6ts5]], [[6ts6]] - hFXIa (mutant) + inhibitor<br /> | **[[5e2o]], [[5exm]], [[5tks]], [[5tkt]], [[5wb6]], [[6ts4]], [[6ts5]], [[6ts6]], [[6usy]], [[7v0z]], [[7v10]], [[7v11]], [[7v12]], [[7v13]], [[7v14]], [[7v15]], [[7v16]], [[7v17]], [[7v18]] - hFXIa (mutant) + inhibitor<br /> | ||
**[[4cr5]], [[4cr9]], [[4cra]], [[4crb]], [[4cre]], [[4crf]], [[1ztl]], [[4ty7]], [[4wxi]], [[4d76]], [[4d7f]], [[4d7g]], [[5e2p]], [[6ts7]], [[6vlv]] - hFXIa (mutant) + quinolin inhibitor<br /> | **[[4cr5]], [[4cr9]], [[4cra]], [[4crb]], [[4cre]], [[4crf]], [[1ztl]], [[4ty7]], [[4wxi]], [[4d76]], [[4d7f]], [[4d7g]], [[5e2p]], [[6ts7]], [[6vlv]] - hFXIa (mutant) + quinolin inhibitor<br /> | ||
**[[4y8y]] - hFXIa + tetrazol inhibitor<br /> | **[[4y8y]] - hFXIa + tetrazol inhibitor<br /> | ||
**[[4crc]], [[4crd]], [[3sor]], [[1zpc]], [[3sos]], [[4x6o]], [[5exn]], [[5tku]], [[6c0s]] - hFXIa (mutant) + tetrazol inhibitor<br /> | **[[4crc]], [[4crd]], [[3sor]], [[1zpc]], [[3sos]], [[4x6o]], [[5exn]], [[5tku]], [[6c0s]] - hFXIa (mutant) + tetrazol inhibitor<br /> | ||
**[[6w50]] - hFXIa + pyrimidine inhibitor<br /> | **[[6w50]] - hFXIa + pyrimidine inhibitor<br /> | ||
**[[1ztk]], [[1ztj]], [[1zsl]], [[4crg]] - hFXIa (mutant) + pyrimidine inhibitor<br /> | **[[1ztk]], [[1ztj]], [[1zsl]], [[4crg]], [[7mbo]] - hFXIa (mutant) + pyrimidine inhibitor<br /> | ||
**[[4x6m]], [[4x6p]], [[5exl]] - hFXIa (mutant) + indazole inhibitor<br /> | **[[4x6m]], [[4x6p]], [[5exl]] - hFXIa (mutant) + indazole inhibitor<br /> | ||
**[[4x6n]] - hFXIa (mutant) + indazole inhibitor + peptide<br /> | **[[4x6n]] - hFXIa (mutant) + indazole inhibitor + peptide<br /> | ||
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**[[6aod]], [[6hhc]] - hFXIa light chain (mutant) + antibody<br /> | **[[6aod]], [[6hhc]] - hFXIa light chain (mutant) + antibody<br /> | ||
**[[6twb]], [[6twc]] - hFXIa light chain + peptide<br /> | **[[6twb]], [[6twc]] - hFXIa light chain + peptide<br /> | ||
**[[5q0f]], [[5qqo]] - hFXIa light chain + peptide + inhibitor<br /> | |||
**[[7qot]] - hFXIa heavy chain + kiniogen<br /> | |||
}} | }} | ||
==References== | ==References== | ||
