4a7i

From Proteopedia

(Difference between revisions)

Revision as of 09:04, 21 December 2014

Factor Xa in complex with a potent 2-amino-ethane sulfonamide inhibitor

Structural highlights

4a7i 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:	1wu1, 2j34, 2bq7, 2y5g, 2w3k, 2vwo, 1xka, 1nfw, 2gd4, 2vvv, 2y5f, 2xbx, 1msx, 1lpg, 2vvu, 1p0s, 2g00, 1mq6, 1xkb, 1iqe, 1g2m, 2vh0, 1nfy, 2uwl, 2bok, 1hcg, 1lpz, 2w3i, 2jkh, 1z6e, 2uwp, 2xc4, 2y81, 1g2l, 1nfu, 2xc0, 2bq6, 1fax, 1iqf, 2y7x, 1nl8, 1iqg, 1iqh, 1lqd, 2uwo, 1c5m, 1ioe, 1f0s, 1f0r, 2xby, 2xc5, 2y7z, 1mq5, 2bmg, 1iqn, 2xbv, 2bqw, 1iqm, 1ezq, 2vwl, 2vh6, 1fjs, 1lpk, 2j4i, 2y5h, 1nfx, 2vwn, 1iqj, 2j94, 2j95, 2cji, 2boh, 2j38, 2vvc, 2w26, 1iqi, 2vwm, 1kye, 2y82, 2y80, 1iqk, 2wyj, 1v3x, 2fzz, 2j2u, 2xbw, 2wyg, 1ksn, 1iql
Activity:	Coagulation factor Xa, with EC number 3.4.21.6
Resources:	FirstGlance, OCA, RCSB, PDBsum

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.

Publication Abstract from PubMed

More than just the sum of its parts: The superadditivity effect of fragment linking on DeltaG was quantified by deconstructing two fXa inhibitors with congeneric fragments, but different linkers. By connecting both fragments with a single bond, a high linker contribution DeltaG(link) of -14.0 kJ mol(-1) results, which corresponds to an improvement in affinity by around 2.5 orders of magnitude relative to the sum of fragment DeltaG values.

Fragment deconstruction of small, potent factor xa inhibitors: exploring the superadditivity energetics of fragment linking in protein-ligand complexes.,Nazare M, Matter H, Will DW, Wagner M, Urmann M, Czech J, Schreuder H, Bauer A, Ritter K, Wehner V Angew Chem Int Ed Engl. 2012 Jan 23;51(4):905-11. doi:, 10.1002/anie.201107091. Epub 2011 Dec 21. PMID:22190348^[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
↑ Nazare M, Matter H, Will DW, Wagner M, Urmann M, Czech J, Schreuder H, Bauer A, Ritter K, Wehner V. Fragment deconstruction of small, potent factor xa inhibitors: exploring the superadditivity energetics of fragment linking in protein-ligand complexes. Angew Chem Int Ed Engl. 2012 Jan 23;51(4):905-11. doi:, 10.1002/anie.201107091. Epub 2011 Dec 21. PMID:22190348 doi:10.1002/anie.201107091

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4a7i"

@@ Line 1: / Line 1: @@
-{{STRUCTURE_4a7i|  PDB=4a7i  |  SCENE=  }}
+==Factor Xa in complex with a potent 2-amino-ethane sulfonamide inhibitor==
-===Factor Xa in complex with a potent 2-amino-ethane sulfonamide inhibitor===
+<StructureSection load='4a7i' size='340' side='right' caption='[[4a7i]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
-{{ABSTRACT_PUBMED_22190348}}
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4a7i]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A7I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A7I FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A7I:5-CHLORO-THIOPHENE-2-CARBOXYLIC+ACID+[2-(1--ISOPROPYL-PIPERIDIN-4-YLSULFAMOYL)-ETHYL]-AMIDE'>A7I</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1wu1|1wu1]], [[2j34|2j34]], [[2bq7|2bq7]], [[2y5g|2y5g]], [[2w3k|2w3k]], [[2vwo|2vwo]], [[1xka|1xka]], [[1nfw|1nfw]], [[2gd4|2gd4]], [[2vvv|2vvv]], [[2y5f|2y5f]], [[2xbx|2xbx]], [[1msx|1msx]], [[1lpg|1lpg]], [[2vvu|2vvu]], [[1p0s|1p0s]], [[2g00|2g00]], [[1mq6|1mq6]], [[1xkb|1xkb]], [[1iqe|1iqe]], [[1g2m|1g2m]], [[2vh0|2vh0]], [[1nfy|1nfy]], [[2uwl|2uwl]], [[2bok|2bok]], [[1hcg|1hcg]], [[1lpz|1lpz]], [[2w3i|2w3i]], [[2jkh|2jkh]], [[1z6e|1z6e]], [[2uwp|2uwp]], [[2xc4|2xc4]], [[2y81|2y81]], [[1g2l|1g2l]], [[1nfu|1nfu]], [[2xc0|2xc0]], [[2bq6|2bq6]], [[1fax|1fax]], [[1iqf|1iqf]], [[2y7x|2y7x]], [[1nl8|1nl8]], [[1iqg|1iqg]], [[1iqh|1iqh]], [[1lqd|1lqd]], [[2uwo|2uwo]], [[1c5m|1c5m]], [[1ioe|1ioe]], [[1f0s|1f0s]], [[1f0r|1f0r]], [[2xby|2xby]], [[2xc5|2xc5]], [[2y7z|2y7z]], [[1mq5|1mq5]], [[2bmg|2bmg]], [[1iqn|1iqn]], [[2xbv|2xbv]], [[2bqw|2bqw]], [[1iqm|1iqm]], [[1ezq|1ezq]], [[2vwl|2vwl]], [[2vh6|2vh6]], [[1fjs|1fjs]], [[1lpk|1lpk]], [[2j4i|2j4i]], [[2y5h|2y5h]], [[1nfx|1nfx]], [[2vwn|2vwn]], [[1iqj|1iqj]], [[2j94|2j94]], [[2j95|2j95]], [[2cji|2cji]], [[2boh|2boh]], [[2j38|2j38]], [[2vvc|2vvc]], [[2w26|2w26]], [[1iqi|1iqi]], [[2vwm|2vwm]], [[1kye|1kye]], [[2y82|2y82]], [[2y80|2y80]], [[1iqk|1iqk]], [[2wyj|2wyj]], [[1v3x|1v3x]], [[2fzz|2fzz]], [[2j2u|2j2u]], [[2xbw|2xbw]], [[2wyg|2wyg]], [[1ksn|1ksn]], [[1iql|1iql]]</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=4a7i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a7i OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4a7i RCSB], [http://www.ebi.ac.uk/pdbsum/4a7i PDBsum]</span></td></tr>
+</table>
+== Disease ==
+[[http://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN]] Defects in F10 are the cause of factor X deficiency (FA10D) [MIM:[http://omim.org/entry/227600 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.<ref>PMID:2790181</ref> <ref>PMID:1973167</ref> <ref>PMID:1985698</ref> <ref>PMID:7669671</ref> <ref>PMID:8529633</ref> <ref>PMID:7860069</ref> <ref>PMID:8845463</ref> <ref>PMID:8910490</ref> <ref>PMID:10468877</ref> <ref>PMID:10746568</ref> <ref>PMID:10739379</ref> <ref>PMID:11248282</ref> <ref>PMID:11728527</ref> <ref>PMID:12945883</ref> <ref>PMID:15650540</ref> <ref>PMID:17393015</ref> <ref>PMID:19135706</ref>
+== Function ==
+[[http://www.uniprot.org/uniprot/FA10_HUMAN 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.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+More than just the sum of its parts: The superadditivity effect of fragment linking on DeltaG was quantified by deconstructing two fXa inhibitors with congeneric fragments, but different linkers. By connecting both fragments with a single bond, a high linker contribution DeltaG(link) of -14.0 kJ mol(-1) results, which corresponds to an improvement in affinity by around 2.5 orders of magnitude relative to the sum of fragment DeltaG values.
-==Disease==
+Fragment deconstruction of small, potent factor xa inhibitors: exploring the superadditivity energetics of fragment linking in protein-ligand complexes.,Nazare M, Matter H, Will DW, Wagner M, Urmann M, Czech J, Schreuder H, Bauer A, Ritter K, Wehner V Angew Chem Int Ed Engl. 2012 Jan 23;51(4):905-11. doi:, 10.1002/anie.201107091. Epub 2011 Dec 21. PMID:22190348<ref>PMID:22190348</ref>
-[[http://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN]] Defects in F10 are the cause of factor X deficiency (FA10D) [MIM:[http://omim.org/entry/227600 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.<ref>PMID:2790181</ref><ref>PMID:1973167</ref><ref>PMID:1985698</ref><ref>PMID:7669671</ref><ref>PMID:8529633</ref><ref>PMID:7860069</ref><ref>PMID:8845463</ref><ref>PMID:8910490</ref><ref>PMID:10468877</ref><ref>PMID:10746568</ref><ref>PMID:10739379</ref><ref>PMID:11248282</ref><ref>PMID:11728527</ref><ref>PMID:12945883</ref><ref>PMID:15650540</ref><ref>PMID:17393015</ref><ref>PMID:19135706</ref>
-==Function==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[http://www.uniprot.org/uniprot/FA10_HUMAN 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.
+</div>
-==About this Structure==
-[[4a7i]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A7I OCA].
 ==See Also==
 *[[Factor Xa|Factor Xa]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:022190348</ref><references group="xtra"/><references/>
+__TOC__
+</StructureSection>
 [[Category: Coagulation factor Xa]]
 [[Category: Homo sapiens]]
-[[Category: Bauer, A.]]
+[[Category: Bauer, A]]
-[[Category: Czech, J.]]
+[[Category: Czech, J]]
-[[Category: Matter, H.]]
+[[Category: Matter, H]]
-[[Category: Nazare, M.]]
+[[Category: Nazare, M]]
-[[Category: Ritter, K.]]
+[[Category: Ritter, K]]
-[[Category: Schreuder, H.]]
+[[Category: Schreuder, H]]
-[[Category: Urmann, M.]]
+[[Category: Urmann, M]]
-[[Category: Wagner, M.]]
+[[Category: Wagner, M]]
-[[Category: Wehner, V.]]
+[[Category: Wehner, V]]
-[[Category: Will, D W.]]
+[[Category: Will, D W]]
 [[Category: Blood coagulation factor]]
 [[Category: Calcium- binding]]

4a7i

From Proteopedia

Revision as of 09:04, 21 December 2014

Factor Xa in complex with a potent 2-amino-ethane sulfonamide inhibitor

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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