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5eok

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Revision as of 07:07, 22 April 2020

Human Plasma Coagulation Factor XI in complex with peptide P39

Structural highlights

5eok is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	F11 (HUMAN)
Activity:	Coagulation factor XIa, with EC number 3.4.21.27
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[FA11_HUMAN] Defects in F11 are the cause of factor XI deficiency (FA11D) [MIM:612416]; also known as plasma thromboplastin antecedent deficiency or Rosenthal syndrome. It is a hemorrhagic disease characterized by reduced levels and activity of factor XI resulting in moderate bleeding symptoms, usually occurring after trauma or surgery. Patients usually do not present spontaneous bleeding but women can present with menorrhagia. Hemorrhages are usually moderate.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] ^[12] ^[13] ^[14] ^[15] ^[16] ^[17] ^[18] ^[19] ^[20]

Function

[FA11_HUMAN] Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX.

Publication Abstract from PubMed

Factor XI (FXI) is the zymogen of factor XIa (FXIa) which cleaves factor IX in the intrinsic pathway of coagulation. FXI is known to exist as a dimer and form interactions with multiple proteins via its four apple domains in the "saucer section" of the enzyme however to date, no complex crystal structure has been described. To investigate protein interactions of FXI a large random peptide library consisting of 106-107peptides was screened for FXI binding and this identified a series of FXI binding motifs containing the signature Asp-Phe-Pro (DFP) tripeptide. Motifs containing this core tripeptide were found in diverse proteins including the known ligand high molecular weight kininogen (HK) as well as extracellular matrix proteins laminin and collagen V. To define the binding site on FXI we determined the crystal structure of FXI in complex with the HK derived peptide NPISDFPDT. This revealed the location of the DFP peptide bound to the FXI apple 2 domain and central to the interaction the DFP phenylalanine side chain inserts into a major hydrophobic pocket in the apple 2 domain and the isoleucine occupies a flanking minor pocket. Two further structures of FXI in complex with the laminin derived peptide EFPDFPand a DFP peptide from the random screen demonstrated binding in the same pocket although in a slightly different conformation, thus revealing some flexibility in the molecular interactions of the FXI apple 2 domain.

A novel DFP tripeptide motif interacts with the coagulation factor XI apple 2 domain.,Wong SS, Ostergaard S, Hall G, Li C, Williams PM, Stennicke H, Emsley J Blood. 2016 Mar 22. pii: blood-2015-10-676122. PMID:27006387^[21]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Asakai R, Chung DW, Ratnoff OD, Davie EW. Factor XI (plasma thromboplastin antecedent) deficiency in Ashkenazi Jews is a bleeding disorder that can result from three types of point mutations. Proc Natl Acad Sci U S A. 1989 Oct;86(20):7667-71. PMID:2813350
↑ Meijers JC, Davie EW, Chung DW. Expression of human blood coagulation factor XI: characterization of the defect in factor XI type III deficiency. Blood. 1992 Mar 15;79(6):1435-40. PMID:1547342
↑ Pugh RE, McVey JH, Tuddenham EG, Hancock JF. Six point mutations that cause factor XI deficiency. Blood. 1995 Mar 15;85(6):1509-16. PMID:7888672
↑ Imanaka Y, Lal K, Nishimura T, Bolton-Maggs PH, Tuddenham EG, McVey JH. Identification of two novel mutations in non-Jewish factor XI deficiency. Br J Haematol. 1995 Aug;90(4):916-20. PMID:7669672
↑ Wistinghausen B, Reischer A, Oddoux C, Ostrer H, Nardi M, Karpatkin M. Severe factor XI deficiency in an Arab family associated with a novel mutation in exon 11. Br J Haematol. 1997 Dec;99(3):575-7. PMID:9401068
↑ Martincic D, Zimmerman SA, Ware RE, Sun MF, Whitlock JA, Gailani D. Identification of mutations and polymorphisms in the factor XI genes of an African American family by dideoxyfingerprinting. Blood. 1998 Nov 1;92(9):3309-17. PMID:9787168
↑ Alhaq A, Mitchell M, Sethi M, Rahman S, Flynn G, Boulton P, Caeno G, Smith M, Savidge G. Identification of a novel mutation in a non-Jewish factor XI deficient kindred. Br J Haematol. 1999 Jan;104(1):44-9. PMID:10027710
↑ Mitchell M, Cutler J, Thompson S, Moore G, Jenkins Ap Rees E, Smith M, Savidge G, Alhaq A. Heterozygous factor XI deficiency associated with three novel mutations. Br J Haematol. 1999 Dec;107(4):763-5. PMID:10606881
↑ Zivelin A, Bauduer F, Ducout L, Peretz H, Rosenberg N, Yatuv R, Seligsohn U. Factor XI deficiency in French Basques is caused predominantly by an ancestral Cys38Arg mutation in the factor XI gene. Blood. 2002 Apr 1;99(7):2448-54. PMID:11895778
↑ Kravtsov DV, Wu W, Meijers JC, Sun MF, Blinder MA, Dang TP, Wang H, Gailani D. Dominant factor XI deficiency caused by mutations in the factor XI catalytic domain. Blood. 2004 Jul 1;104(1):128-34. Epub 2004 Mar 16. PMID:15026311 doi:10.1182/blood-2003-10-3530
↑ Dai L, Mitchell M, Carson P, Creagh D, Cutler J, Savidge G, Alhaq A. Severe factor XI deficiency caused by compound heterozygosity. Br J Haematol. 2004 Jun;125(6):817-8. PMID:15180874 doi:10.1111/j.1365-2141.2004.04979.x
↑ Hill M, McLeod F, Franks H, Gordon B, Dolan G. Genetic analysis in FXI deficiency: six novel mutations and the use of a polymerase chain reaction-based test to define a whole gene deletion. Br J Haematol. 2005 Jun;129(6):825-9. PMID:15953011 doi:10.1111/j.1365-2141.2005.05536.x
↑ Quelin F, Mathonnet F, Potentini-Esnault C, Trigui N, Peynet J, Bastenaire B, Guillon L, Bigel ML, Sauger A, Mazurier C, de Mazancourt P. Identification of five novel mutations in the factor XI gene (F11) of patients with factor XI deficiency. Blood Coagul Fibrinolysis. 2006 Jan;17(1):69-73. PMID:16607084 doi:10.1097/01.mbc.0000198054.50257.96
↑ Fard-Esfahani P, Lari GR, Ravanbod S, Mirkhani F, Allahyari M, Rassoulzadegan M, Ala F. Seven novel point mutations in the F11 gene in Iranian FXI-deficient patients. Haemophilia. 2008 Jan;14(1):91-5. Epub 2007 Nov 13. PMID:18005151 doi:10.1111/j.1365-2516.2007.01593.x
↑ Kim J, Song J, Lyu CJ, Kim YR, Oh SH, Choi YC, Yoo JH, Choi JR, Kim H, Lee KA. Population-specific spectrum of the F11 mutations in Koreans: evidence for a founder effect. Clin Genet. 2012 Aug;82(2):180-6. doi: 10.1111/j.1399-0004.2011.01732.x. Epub, 2011 Jun 30. PMID:21668437 doi:10.1111/j.1399-0004.2011.01732.x
↑ Dai L, Rangarajan S, Mitchell M. Three dominant-negative mutations in factor XI-deficient patients. Haemophilia. 2011 Sep;17(5):e919-22. doi: 10.1111/j.1365-2516.2011.02519.x. Epub , 2011 Apr 3. PMID:21457405 doi:10.1111/j.1365-2516.2011.02519.x
↑ Lee JH, Cho HS, Hyun MS, Kim HY, Kim HJ. A novel missense mutation Asp506Gly in Exon 13 of the F11 gene in an asymptomatic Korean woman with mild factor XI deficiency. Korean J Lab Med. 2011 Oct;31(4):290-3. doi: 10.3343/kjlm.2011.31.4.290. Epub, 2011 Oct 3. PMID:22016685 doi:10.3343/kjlm.2011.31.4.290
↑ Tirefort Y, Uhr MR, Neerman-Arbez M, de Moerloose P. Identification of a novel F11 missense mutation (Ile463Ser) in a family with congenital factor XI deficiency. Blood Coagul Fibrinolysis. 2012 Apr;23(3):251-2. doi:, 10.1097/MBC.0b013e32834ea02a. PMID:22322133 doi:10.1097/MBC.0b013e32834ea02a
↑ Girolami A, Scarparo P, Bonamigo E, Santarossa L, Cristiani A, Moro S, Lombardi AM. A cluster of factor XI-deficient patients due to a new mutation (Ile 436 Lys) in northeastern Italy. Eur J Haematol. 2012 Mar;88(3):229-36. doi: 10.1111/j.1600-0609.2011.01723.x., Epub 2011 Nov 17. PMID:21999818 doi:10.1111/j.1600-0609.2011.01723.x
↑ Gueguen P, Chauvin A, Quemener-Redon S, Pan-Petesch B, Ferec C, Abgrall JF, Le Marechal C. Revisiting the molecular epidemiology of factor XI deficiency: nine new mutations and an original large 4qTer deletion in western Brittany (France). Thromb Haemost. 2012 Jan;107(1):44-50. doi: 10.1160/TH11-06-0415. Epub 2011 Dec, 8. PMID:22159456 doi:10.1160/TH11-06-0415
↑ Wong SS, Ostergaard S, Hall G, Li C, Williams PM, Stennicke H, Emsley J. A novel DFP tripeptide motif interacts with the coagulation factor XI apple 2 domain. Blood. 2016 Mar 22. pii: blood-2015-10-676122. PMID:27006387 doi:http://dx.doi.org/10.1182/blood-2015-10-676122

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5eok"

@@ Line 1: / Line 1: @@
 ==Human Plasma Coagulation Factor XI in complex with peptide P39==
-<StructureSection load='5eok' size='340' side='right' caption='[[5eok]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+<StructureSection load='5eok' size='340' side='right'caption='[[5eok]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5eok]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EOK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EOK FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5eok]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EOK OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5EOK FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">F11 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Coagulation_factor_XIa Coagulation factor XIa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.27 3.4.21.27] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5eok FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eok OCA], [http://pdbe.org/5eok PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5eok RCSB], [http://www.ebi.ac.uk/pdbsum/5eok PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5eok ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5eok FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eok OCA], [http://pdbe.org/5eok PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5eok RCSB], [http://www.ebi.ac.uk/pdbsum/5eok PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5eok ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 26: / Line 27: @@
 </StructureSection>
 [[Category: Coagulation factor XIa]]
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Emsley, J]]
 [[Category: Hall, G]]
@@ Line 35: / Line 38: @@
 [[Category: Coagulation fxi]]
 [[Category: Complex]]
-[[Category: Human]]
 [[Category: Hydrolase]]
 [[Category: Plasma]]

5eok

From Proteopedia

Revision as of 07:07, 22 April 2020

Human Plasma Coagulation Factor XI in complex with peptide P39

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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