1xx9

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (07:39, 30 October 2024) (edit) (undo)
 
(7 intermediate revisions not shown.)
Line 1: Line 1:
-
{{STRUCTURE_1xx9| PDB=1xx9 | SCENE= }}
 
-
===Crystal Structure of the FXIa Catalytic Domain in Complex with EcotinM84R===
 
-
{{ABSTRACT_PUBMED_15545266}}
 
-
==Disease==
+
==Crystal Structure of the FXIa Catalytic Domain in Complex with EcotinM84R==
-
[[http://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN]] Defects in F11 are the cause of factor XI deficiency (FA11D) [MIM:[http://omim.org/entry/612416 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.<ref>PMID:2813350</ref><ref>PMID:1547342</ref><ref>PMID:7888672</ref><ref>PMID:7669672</ref><ref>PMID:9401068</ref><ref>PMID:9787168</ref><ref>PMID:10027710</ref><ref>PMID:10606881</ref><ref>PMID:11895778</ref><ref>PMID:15026311</ref><ref>PMID:15180874</ref><ref>PMID:15953011</ref><ref>PMID:16607084</ref><ref>PMID:18005151</ref><ref>PMID:21668437</ref><ref>PMID:21457405</ref><ref>PMID:22016685</ref><ref>PMID:22322133</ref><ref>PMID:21999818</ref><ref>PMID:22159456</ref>
+
<StructureSection load='1xx9' size='340' side='right'caption='[[1xx9]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[1xx9]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XX9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XX9 FirstGlance]. <br>
 +
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
 +
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1xx9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xx9 OCA], [https://pdbe.org/1xx9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xx9 RCSB], [https://www.ebi.ac.uk/pdbsum/1xx9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xx9 ProSAT]</span></td></tr>
 +
</table>
 +
== Disease ==
 +
[https://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN] Defects in F11 are the cause of factor XI deficiency (FA11D) [MIM:[https://omim.org/entry/612416 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.<ref>PMID:2813350</ref> <ref>PMID:1547342</ref> <ref>PMID:7888672</ref> <ref>PMID:7669672</ref> <ref>PMID:9401068</ref> <ref>PMID:9787168</ref> <ref>PMID:10027710</ref> <ref>PMID:10606881</ref> <ref>PMID:11895778</ref> <ref>PMID:15026311</ref> <ref>PMID:15180874</ref> <ref>PMID:15953011</ref> <ref>PMID:16607084</ref> <ref>PMID:18005151</ref> <ref>PMID:21668437</ref> <ref>PMID:21457405</ref> <ref>PMID:22016685</ref> <ref>PMID:22322133</ref> <ref>PMID:21999818</ref> <ref>PMID:22159456</ref>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN] Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX.
 +
== Evolutionary Conservation ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xx/1xx9_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1xx9 ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Thrombosis can lead to life-threatening conditions such as acute myocardial infarction, pulmonary embolism, and stroke. Although commonly used anti-coagulant drugs, such as low molecular weight heparin and warfarin, are effective, they carry a significant risk of inducing severe bleeding complications, and there is a need for safer drugs. Activated Factor XI (FXIa) is a key enzyme in the amplification phase of the coagulation cascade. Anti-human FXI antibody significantly reduces thrombus growth in a baboon thrombosis model without bleeding problems (Gruber, A., and Hanson, S. R. (2003) Blood 102, 953-955). Therefore, FXIa is a potential target for anti-thrombosis therapy. To determine the structure of FXIa, we derived a recombinant catalytic domain of FXI, consisting of residues 370-607 (rhFXI370-607). Here we report the first crystal structure of rhFXI370-607 in complex with a substitution mutant of ecotin, a panserine protease protein inhibitor secreted by Escherichia coli, to 2.2 A resolution. The presence of ecotin not only assisted in the crystallization of the enzyme but also revealed unique structural features in the active site of FXIa. Subsequently, the sequence from P5 to P2' in ecotin was mutated to the FXIa substrate sequence, and the structures of the rhFXI370-607-ecotin mutant complexes were determined. These structures provide us with an understanding of substrate binding interactions of FXIa, the structural information essential for the structure-based design of FXIa-selective inhibitors.
-
==Function==
+
Crystal structures of the FXIa catalytic domain in complex with ecotin mutants reveal substrate-like interactions.,Jin L, Pandey P, Babine RE, Gorga JC, Seidl KJ, Gelfand E, Weaver DT, Abdel-Meguid SS, Strickler JE J Biol Chem. 2005 Feb 11;280(6):4704-12. Epub 2004 Nov 15. PMID:15545266<ref>PMID:15545266</ref>
-
[[http://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN]] Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX. [[http://www.uniprot.org/uniprot/ECOT_ECOLI ECOT_ECOLI]] General inhibitor of pancreatic serine proteases: inhibits chymotrypsin, trypsin, elastases, factor X, kallikrein as well as a variety of other proteases. The strength of inhibition does not appear to be correlated with a particular protease specificity.[HAMAP-Rule:MF_00706]
+
-
==About this Structure==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[1xx9]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XX9 OCA].
+
</div>
 +
<div class="pdbe-citations 1xx9" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
*[[Ecotin|Ecotin]]
*[[Ecotin|Ecotin]]
-
*[[Factor XIa|Factor XIa]]
+
*[[Factor XIa 3D structures|Factor XIa 3D structures]]
-
 
+
== References ==
-
==Reference==
+
<references/>
-
<ref group="xtra">PMID:015545266</ref><references group="xtra"/><references/>
+
__TOC__
-
[[Category: Coagulation factor XIa]]
+
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Abdel-Meguid, S S.]]
+
[[Category: Large Structures]]
-
[[Category: Babine, R E.]]
+
[[Category: Abdel-Meguid SS]]
-
[[Category: Gelfand, E.]]
+
[[Category: Babine RE]]
-
[[Category: Gorga, J C.]]
+
[[Category: Gelfand E]]
-
[[Category: Jin, L.]]
+
[[Category: Gorga JC]]
-
[[Category: Pandey, P.]]
+
[[Category: Jin L]]
-
[[Category: Seidl, K J.]]
+
[[Category: Pandey P]]
-
[[Category: Strickler, J E.]]
+
[[Category: Seidl KJ]]
-
[[Category: Weaver, D T.]]
+
[[Category: Strickler JE]]
-
[[Category: Blood clotting-hydrolase inhibitor complex]]
+
[[Category: Weaver DT]]
-
[[Category: Catalytic domain]]
+
-
[[Category: Ecotin]]
+
-
[[Category: Fxia]]
+
-
[[Category: Serine protein]]
+

Current revision

Crystal Structure of the FXIa Catalytic Domain in Complex with EcotinM84R

PDB ID 1xx9

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1xx9"
Personal tools