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2j2u

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Revision as of 06:52, 11 July 2018

CRYSTAL STRUCTURE OF A HUMAN FACTOR XA INHIBITOR COMPLEX

Structural highlights

2j2u is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	1c5m, 1ezq, 1f0r, 1f0s, 1fax, 1fjs, 1fxy, 1g2l, 1g2m, 1hcg, 1ioe, 1iqe, 1iqf, 1iqg, 1iqh, 1iqi, 1iqj, 1iqk, 1iql, 1iqm, 1iqn, 1ksn, 1kye, 1lpg, 1lpk, 1lpz, 1lqd, 1mq5, 1mq6, 1msx, 1nfu, 1nfw, 1nfx, 1nfy, 1nl8, 1p0s, 1v3x, 1wu1, 1xka, 1xkb, 1z6e, 2bmg, 2boh, 2bok, 2bq6, 2bq7, 2bqw, 2cji, 2fzz, 2gd4
Activity:	Coagulation factor Xa, with EC number 3.4.21.6
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[FA10_HUMAN] Defects in F10 are the cause of factor X deficiency (FA10D) [MIM:227600]. A hemorrhagic disease with variable presentation. Affected individuals can manifest prolonged nasal and mucosal hemorrhage, menorrhagia, hematuria, and occasionally hemarthrosis. Some patients do not have clinical bleeding diathesis.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] ^[12] ^[13] ^[14] ^[15] ^[16] ^[17]

Function

[FA10_HUMAN] Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Torsional scans of sulfonamide S-C bonds in small model systems of a series of arylsulfonamide factor Xa inhibitors were performed in order to investigate if conformational effects can help to rationalise the observed SAR. Computational results were in good agreement with the experimental data indicating that the sulfonamide conformation plays an important role in determining the activity in this particular series of factor Xa inhibitors.

Arylsulfonamides: a study of the relationship between activity and conformational preferences for a series of factor Xa inhibitors.,Senger S, Convery MA, Chan C, Watson NS Bioorg Med Chem Lett. 2006 Nov 15;16(22):5731-5. Epub 2006 Sep 18. PMID:16982192^[18]

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

References

↑ Reddy SV, Zhou ZQ, Rao KJ, Scott JP, Watzke H, High KA, Jagadeeswaran P. Molecular characterization of human factor XSan Antonio. Blood. 1989 Oct;74(5):1486-90. PMID:2790181
↑ Watzke HH, Lechner K, Roberts HR, Reddy SV, Welsch DJ, Friedman P, Mahr G, Jagadeeswaran P, Monroe DM, High KA. Molecular defect (Gla+14----Lys) and its functional consequences in a hereditary factor X deficiency (factor X "Vorarlberg"). J Biol Chem. 1990 Jul 15;265(20):11982-9. PMID:1973167
↑ James HL, Girolami A, Fair DS. Molecular defect in coagulation factor XFriuli results from a substitution of serine for proline at position 343. Blood. 1991 Jan 15;77(2):317-23. PMID:1985698
↑ Marchetti G, Castaman G, Pinotti M, Lunghi B, Di Iasio MG, Ruggieri M, Rodeghiero F, Bernardi F. 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. Br J Haematol. 1995 Aug;90(4):910-5. PMID:7669671
↑ Bezeaud A, Miyata T, Helley D, Zeng YZ, Kato H, Aillaud MF, Juhan-Vague I, Guillin MC. Functional consequences of the Ser334-->Pro mutation in a human factor X variant (factor XMarseille). Eur J Biochem. 1995 Nov 15;234(1):140-7. PMID:8529633
↑ Kim DJ, Thompson AR, James HL. Factor XKetchikan: a variant molecule in which Gly replaces a Gla residue at position 14 in the light chain. Hum Genet. 1995 Feb;95(2):212-4. PMID:7860069
↑ Messier TL, Wong CY, Bovill EG, Long GL, Church WR. Factor X Stockton: a mild bleeding diathesis associated with an active site mutation in factor X. Blood Coagul Fibrinolysis. 1996 Jan;7(1):5-14. PMID:8845463
↑ Rudolph AE, Mullane MP, Porche-Sorbet R, Tsuda S, Miletich JP. Factor XSt. Louis II. Identification of a glycine substitution at residue 7 and characterization of the recombinant protein. J Biol Chem. 1996 Nov 8;271(45):28601-6. PMID:8910490
↑ Zama T, Murata M, Watanabe R, Yokoyama K, Moriki T, Ambo H, Murakami H, Kikuchi M, Ikeda Y. A family with hereditary factor X deficiency with a point mutation Gla32 to Gln in the Gla domain (factor X Tokyo). Br J Haematol. 1999 Sep;106(3):809-11. PMID:10468877
↑ Millar DS, Elliston L, Deex P, Krawczak M, Wacey AI, Reynaud J, Nieuwenhuis HK, Bolton-Maggs P, Mannucci PM, Reverter JC, Cachia P, Pasi KJ, Layton DM, Cooper DN. Molecular analysis of the genotype-phenotype relationship in factor X deficiency. Hum Genet. 2000 Feb;106(2):249-57. PMID:10746568
↑ Forberg E, Huhmann I, Jimenez-Boj E, Watzke HH. The impact of Glu102Lys on the factor X function in a patient with a doubly homozygous factor X deficiency (Gla14Lys and Glu102Lys). Thromb Haemost. 2000 Feb;83(2):234-8. PMID:10739379
↑ Simioni P, Vianello F, Kalafatis M, Barzon L, Ladogana S, Paolucci P, Carotenuto M, Dal Bello F, Palu G, Girolami A. A dysfunctional factor X (factor X San Giovanni Rotondo) present at homozygous and double heterozygous level: identification of a novel microdeletion (delC556) and missense mutation (Lys(408)-->Asn) in the factor X gene. A study of an Italian family. Thromb Res. 2001 Feb 15;101(4):219-30. PMID:11248282
↑ Vianello F, Lombardi AM, Boldrin C, Luni S, Girolami A. A new factor X defect (factor X Padua 3): a compound heterozygous between true deficiency (Gly(380)-->Arg) and an abnormality (Ser(334)-->Pro). Thromb Res. 2001 Nov 15;104(4):257-64. PMID:11728527
↑ Vianello F, Lombardi AM, Bello FD, Palu G, Zanon E, Girolami A. A novel type I factor X variant (factor X Cys350Phe) due to loss of a disulfide bond in the catalytic domain. Blood Coagul Fibrinolysis. 2003 Jun;14(4):401-5. PMID:12945883
↑ Isshiki I, Favier R, Moriki T, Uchida T, Ishihara H, Van Dreden P, Murata M, Ikeda Y. Genetic analysis of hereditary factor X deficiency in a French patient of Sri Lankan ancestry: in vitro expression study identified Gly366Ser substitution as the molecular basis of the dysfunctional factor X. Blood Coagul Fibrinolysis. 2005 Jan;16(1):9-16. PMID:15650540
↑ Al-Hilali A, Wulff K, Abdel-Razeq H, Saud KA, Al-Gaili F, Herrmann FH. Analysis of the novel factor X gene mutation Glu51Lys in two families with factor X-Riyadh anomaly. Thromb Haemost. 2007 Apr;97(4):542-5. PMID:17393015
↑ Chafa O, Tagzirt M, Tapon-Bretaudiere J, Reghis A, Fischer AM, LeBonniec BF. Characterization of a homozygous Gly11Val mutation in the Gla domain of coagulation factor X. Thromb Res. 2009 May;124(1):144-8. doi: 10.1016/j.thromres.2008.11.018. Epub 2009, Jan 10. PMID:19135706 doi:10.1016/j.thromres.2008.11.018
↑ Senger S, Convery MA, Chan C, Watson NS. Arylsulfonamides: a study of the relationship between activity and conformational preferences for a series of factor Xa inhibitors. Bioorg Med Chem Lett. 2006 Nov 15;16(22):5731-5. Epub 2006 Sep 18. PMID:16982192 doi:http://dx.doi.org/10.1016/j.bmcl.2006.08.092

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2j2u"

@@ Line 1: / Line 1: @@
 ==CRYSTAL STRUCTURE OF A HUMAN FACTOR XA INHIBITOR COMPLEX==
 <StructureSection load='2j2u' size='340' side='right' caption='[[2j2u]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1c5m|1c5m]], [[1ezq|1ezq]], [[1f0r|1f0r]], [[1f0s|1f0s]], [[1fax|1fax]], [[1fjs|1fjs]], [[1fxy|1fxy]], [[1g2l|1g2l]], [[1g2m|1g2m]], [[1hcg|1hcg]], [[1ioe|1ioe]], [[1iqe|1iqe]], [[1iqf|1iqf]], [[1iqg|1iqg]], [[1iqh|1iqh]], [[1iqi|1iqi]], [[1iqj|1iqj]], [[1iqk|1iqk]], [[1iql|1iql]], [[1iqm|1iqm]], [[1iqn|1iqn]], [[1ksn|1ksn]], [[1kye|1kye]], [[1lpg|1lpg]], [[1lpk|1lpk]], [[1lpz|1lpz]], [[1lqd|1lqd]], [[1mq5|1mq5]], [[1mq6|1mq6]], [[1msx|1msx]], [[1nfu|1nfu]], [[1nfw|1nfw]], [[1nfx|1nfx]], [[1nfy|1nfy]], [[1nl8|1nl8]], [[1p0s|1p0s]], [[1v3x|1v3x]], [[1wu1|1wu1]], [[1xka|1xka]], [[1xkb|1xkb]], [[1z6e|1z6e]], [[2bmg|2bmg]], [[2boh|2boh]], [[2bok|2bok]], [[2bq6|2bq6]], [[2bq7|2bq7]], [[2bqw|2bqw]], [[2cji|2cji]], [[2fzz|2fzz]], [[2gd4|2gd4]]</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_Xa Coagulation factor Xa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.6 3.4.21.6] </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=2j2u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j2u OCA], [http://pdbe.org/2j2u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2j2u RCSB], [http://www.ebi.ac.uk/pdbsum/2j2u PDBsum]</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=2j2u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j2u OCA], [http://pdbe.org/2j2u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2j2u RCSB], [http://www.ebi.ac.uk/pdbsum/2j2u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2j2u ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 16: / Line 17: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/j2/2j2u_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/j2/2j2u_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 45: / Line 46: @@
 [[Category: Watson, N S]]
 [[Category: Blood coagulation]]
+[[Category: Calcium]]
 [[Category: Complex]]
 [[Category: Egf-like domain]]
@@ Line 52: / Line 54: @@
 [[Category: Hydrolase]]
 [[Category: Hydroxylation]]
+[[Category: Polymorphism]]
 [[Category: Protease]]
 [[Category: Serine protease]]
 [[Category: Zymogen]]

2j2u

From Proteopedia

Revision as of 06:52, 11 July 2018

CRYSTAL STRUCTURE OF A HUMAN FACTOR XA INHIBITOR COMPLEX

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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