Factor X: Diferenzas entre revisións

Explorar o historial de forma interactiva

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Revisión como estaba o 2 de setembro de 2018 ás 12:24


PDB 1c5m
F10
Identificadores
Símbolo	F10
Símbolos alt.	FX, FXA, factor de coagulación X
Entrez	2159
OMIM	613872
RefSeq	NP_000495
UniProt	P00742
Outros datos
Locus	Cr. 13 q34:(113.12 – 113.15 Mb)

Non se debe confundir co factor X de crecemento para o cultivo da bacteria Haemophilus influenzae correspondente á protroporfirina IX ou hemina.

O factor X (factor dez) de coagulación, tamén chamado factor de Stuart–Prower, é un encima (EC 3.4.21.6) da fervenza de coagulación do sangue. É unha serina endopeptidase (protease do grupo S1, clan PA). O factor X é sintetizado no fígado e require vitamina K para a súa síntese.

O factor X é activado por hidrólise dando lugar ao factor Xa por acción do factor IX (co seu cofactor o factor VIII nun complexo chamado Xase intrínseca) ou polo factor VII (co seu cofactor factor tisular, formando un complexo chamado Xase extrínseca). É, por tanto, o primeiro membro da vía común final ou vía da trombina da coagulación.

Actúa clivando a protrombina en dous sitios (un enlace Arg-Thr e outro Arg-Ile), orixinando a trombina activa. Este proceso está optimizado cando o factor Xa está en acomplexado co cofactor V activado no complexo da protrombinase.

O factor Xa é inactivado polo inhibidor da protease dependente da proteína Z (ZPI), un inhibidor da serina protease (serpina). A afinidade desta proteína polo factor Xa multiplícase por mil en presenza da proteína Z, mentresque non cómpre proteína Z par a inactivación do factor XI. Os defectos na proteína Z causan un incremento da actividade do factor Xa e unha propensión á trombose.

A vida media do factor X é de entre 40 e 45 horas.

Estrutura

Historia

Científicos estadounidenses e británicos describiron a deficiencia de factor X independentemente en 1953 e 1956, respectivamente. Igual que algúns outros factores de cosgulación, o factor foi inicialmente nomeado polo nome dos pacientes nos que se atopou a deficiencia, chamados Rufus Stuart (1921) e Audrey Prower (1934), polo que se denominou factor Stuart-Prower.

Interaccións

O factor X presenta interaccións co inhibidor da vía do factor tisular.^[1]

Notas

↑ Broze GJ, Warren LA, Novotny WF, Higuchi DA, Girard JJ, Miletich JP (February 1988). "The lipoprotein-associated coagulation inhibitor that inhibits the factor VII-tissue factor complex also inhibits factor Xa: insight into its possible mechanism of action". Blood 71 (2): 335–43. PMID 3422166.

Véxase tamén

Ligazóns externas

A base de datos en liña MEROPS para peptidases e os seus inhibidores: S01.216
Modelo:EMedicine
Deficiencia de factor X

Bibliografía

Cooper DN, Millar DS, Wacey A, Pemberton S, Tuddenham EG (July 1997). "Inherited factor X deficiency: molecular genetics and pathophysiology". Thrombosis and Haemostasis 78 (1): 161–72. PMID 9198147.
Hassan HJ, Leonardi A, Chelucci C, Mattia G, Macioce G, Guerriero R, Russo G, Mannucci PM, Peschle C (September 1990). "Blood coagulation factors in human embryonic-fetal development: preferential expression of the FVII/tissue factor pathway". Blood 76 (6): 1158–64. PMID 1698100.
Messier TL, Pittman DD, Long GL, Kaufman RJ, Church WR (March 1991). "Cloning and expression in COS-1 cells of a full-length cDNA encoding human coagulation factor X". Gene 99 (2): 291–4. PMID 1902434. doi:10.1016/0378-1119(91)90141-W.
Krishnaswamy S (March 1990). "Prothrombinase complex assembly. Contributions of protein-protein and protein-membrane interactions toward complex formation". The Journal of Biological Chemistry 265 (7): 3708–18. PMID 2303476.
España F, Berrettini M, Griffin JH (August 1989). "Purification and characterization of plasma protein C inhibitor". Thrombosis Research 55 (3): 369–84. PMID 2551064. doi:10.1016/0049-3848(89)90069-8.
Fung MR, Hay CW, MacGillivray RT (June 1985). "Characterization of an almost full-length cDNA coding for human blood coagulation factor X". Proceedings of the National Academy of Sciences of the United States of America 82 (11): 3591–5. PMC 397831. PMID 2582420. doi:10.1073/pnas.82.11.3591.
Jagadeeswaran P, Reddy SV, Rao KJ, Hamsabhushanam K, Lyman G (December 1989). "Cloning and characterization of the 5' end (exon 1) of the gene encoding human factor X". Gene 84 (2): 517–9. PMID 2612918. doi:10.1016/0378-1119(89)90529-5.
Reddy SV, Zhou ZQ, Rao KJ, Scott JP, Watzke H, High KA, Jagadeeswaran P (October 1989). "Molecular characterization of human factor XSan Antonio". Blood 74 (5): 1486–90. PMID 2790181.
Kaul RK, Hildebrand B, Roberts S, Jagadeeswaran P (1986). "Isolation and characterization of human blood-coagulation factor X cDNA". Gene 41 (2-3): 311–4. PMID 3011603. doi:10.1016/0378-1119(86)90112-5.
Broze GJ, Warren LA, Novotny WF, Higuchi DA, Girard JJ, Miletich JP (February 1988). "The lipoprotein-associated coagulation inhibitor that inhibits the factor VII-tissue factor complex also inhibits factor Xa: insight into its possible mechanism of action". Blood 71 (2): 335–43. PMID 3422166.
Gilgenkrantz S, Briquel ME, André E, Alexandre P, Jalbert P, Le Marec B, Pouzol P, Pommereuil M (1986). "Structural genes of coagulation factors VII and X located on 13q34". Annales De Genetique 29 (1): 32–5. PMID 3487272.
Leytus SP, Foster DC, Kurachi K, Davie EW (September 1986). "Gene for human factor X: a blood coagulation factor whose gene organization is essentially identical with that of factor IX and protein C". Biochemistry 25 (18): 5098–102. PMID 3768336. doi:10.1021/bi00366a018.
Leytus SP, Chung DW, Kisiel W, Kurachi K, Davie EW (June 1984). "Characterization of a cDNA coding for human factor X". Proceedings of the National Academy of Sciences of the United States of America 81 (12): 3699–702. PMC 345286. PMID 6587384. doi:10.1073/pnas.81.12.3699.
McMullen BA, Fujikawa K, Kisiel W, Sasagawa T, Howald WN, Kwa EY, Weinstein B (June 1983). "Complete amino acid sequence of the light chain of human blood coagulation factor X: evidence for identification of residue 63 as beta-hydroxyaspartic acid". Biochemistry 22 (12): 2875–84. PMID 6871167. doi:10.1021/bi00281a016.
Marchetti G, Castaman G, Pinotti M, Lunghi B, Di Iasio MG, Ruggieri M, Rodeghiero F, Bernardi F (August 1995). "Molecular bases of CRM+ factor X deficiency: a frequent mutation (Ser334Pro) in the catalytic domain and a substitution (Glu102Lys) in the second EGF-like domain". British Journal of Haematology 90 (4): 910–5. PMID 7669671. doi:10.1111/j.1365-2141.1995.tb05214.x.
Morgenstern KA, Sprecher C, Holth L, Foster D, Grant FJ, Ching A, Kisiel W (March 1994). "Complementary DNA cloning and kinetic characterization of a novel intracellular serine proteinase inhibitor: mechanism of action with trypsin and factor Xa as model proteinases". Biochemistry 33 (11): 3432–41. PMID 8136380. doi:10.1021/bi00177a037.
Heeb MJ, Rosing J, Bakker HM, Fernandez JA, Tans G, Griffin JH (March 1994). "Protein S binds to and inhibits factor Xa". Proceedings of the National Academy of Sciences of the United States of America 91 (7): 2728–32. PMC 43443. PMID 8146182. doi:10.1073/pnas.91.7.2728.
Inoue K, Morita T (November 1993). "Identification of O-linked oligosaccharide chains in the activation peptides of blood coagulation factor X. The role of the carbohydrate moieties in the activation of factor X". European Journal of Biochemistry 218 (1): 153–63. PMID 8243461. doi:10.1111/j.1432-1033.1993.tb18361.x.
Padmanabhan K, Padmanabhan KP, Tulinsky A, Park CH, Bode W, Huber R, Blankenship DT, Cardin AD, Kisiel W (August 1993). "Structure of human des(1-45) factor Xa at 2.2 A resolution". Journal of Molecular Biology 232 (3): 947–66. PMID 8355279. doi:10.1006/jmbi.1993.1441.
Sinha U, Wolf DL (February 1993). "Carbohydrate residues modulate the activation of coagulation factor X". The Journal of Biological Chemistry 268 (5): 3048–51. PMID 8428982.

[pmid3422166-1] Broze GJ, Warren LA, Novotny WF, Higuchi DA, Girard JJ, Miletich JP (February 1988). "The lipoprotein-associated coagulation inhibitor that inhibits the factor VII-tissue factor complex also inhibits factor Xa: insight into its possible mechanism of action". Blood 71 (2): 335–43. PMID 3422166.

[1]

@@ Liña 40: / Liña 40: @@
 <!--
 {{Véxase tamén|Factor IX#Arquitectura de dominios}}
-The first crystal structure of human factor Xa was deposited in May 1993. To date, 191 crystal structures of factor Xa with various inhibitors have been deposited in the protein data bank. The active site of factor Xa is divided into four sub pockets as S1, S2, S3 and S4. The S1 subpocket determines the major component of selectivity and binding. The S2 sub-pocket is small, shallow and not well defined. It merges with the S4 subpocket. The S3 sub-pocket is located on the rim of the S1 pocket and is quite exposed to solvent. The S4 sub-pocket has three ligand binding domains: the "hydrophobic box", the "cationic hole" and the water site. Factor Xa inhibitors generally bind in an L-shaped conformation, where one group of the ligand occupies the anionic S1 pocket lined by residues Asp189, Ser195, and Tyr228, and another group of the ligand occupies the aromatic S4 pocket lined by residues Tyr99, Phe174, and Trp215. Typically, a fairly rigid linker group bridges these two interaction sites.<ref>[http://pharmaxchange.info/presentations/Direct%20FXa%20Inhibitors.html Presentation on Direct Factor Xa Inhibitors]</ref>
+A primeira estrutura cristalina do factor Xa humano foi depositada no ''Protein dat bank'' en maio de 1993. Ata agora, obtivéronse 191 estruturas cristalinas do factor Xa con varios inhibidores. O sitio activo do factor Xa está dividido en catro subpetos denominados S1, S2, S3 e S4. O subpeto S1 determina o compoñente principal para a selectividade e unión. O subpeto S2 é pequeno, pouco profundo e non está ben definido. Fusiónase co subpeto S4. O subpeto S3 está localizado no bordo do subpeto S1 e está bastante exposto ao solvente. O subpeto S4 ten tres dominios de unión de ligandos: a "caixa hidrofóbica", o "burato catiónico" e o sitio pra a auga. Os inhibidores do factor Xa únense xeralmente nunha conformación con forma de L, na que un grupo do [[ligando]] ocupa o subpeto aniónico S1 onde se encontran os residuos Asp189, Ser195 e Tyr228, e outro grupo do ligando ocupa o peto aromático S4 onde se encontran os residuos Tyr99, Phe174 e Trp215. Tipicamente, un grupo enlazador bastante ríxido fai ponte entre estes dous sitios de interacción.<ref>[http://pharmaxchange.info/presentations/Direct%20FXa%20Inhibitors.html Presentation on Direct Factor Xa Inhibitors]</ref>
 == Xenética ==
@@ Liña 46: / Liña 46: @@
 == Papel en enfermidades ==
+<!--
 A [[deficiencia de factor X]] conxénita is very rare (1:1,000,000), and may present with [[epistaxis]] (nosebleeds), [[hemarthrosis]] (bleeding into joints) and gastrointestinal blood loss. Apart from congenital deficiency, low factor X levels may occur occasionally in a number of disease states.  For example, factor X deficiency may be seen in [[amyloidosis]], where factor X is adsorbed to the amyloid fibrils in the vasculature.
@@ Liña 84: / Liña 85: @@
 Recently a new series of specific, direct acting inhibitors of Factor Xa has been developed. These include the drugs [[rivaroxaban]], [[apixaban]], [[betrixaban]], LY517717, [[darexaban]] (YM150), [[edoxaban]] and 813893. These agents have several theoretical advantages over current therapy. They may be given orally. They have rapid onset of action. And they may be more effective against Factor Xa in that they inhibit both free Factor Xa and Factor Xa in the prothrombinase complex.<ref name="ATVB">{{cite journal | vauthors = Turpie AG | title = Oral, direct factor Xa inhibitors in development for the prevention and treatment of thromboembolic diseases | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 27 | issue = 6 | pages = 1238–47 | date = June 2007 | pmid = 17379841 | doi = 10.1161/ATVBAHA.107.139402 }}</ref>
 -->
 == Historia ==
 Científicos estadounidenses e británicos describiron a deficiencia de factor X independentemente en 1953 e 1956, respectivamente. Igual que algúns outros [[factor de coagulación|factores de cosgulación]], o factor foi inicialmente nomeado polo nome dos pacientes nos que se atopou a deficiencia, chamados Rufus Stuart (1921) e Audrey Prower (1934), polo que se denominou factor Stuart-Prower.