1zjd

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (08:58, 6 November 2024) (edit) (undo)
 
(7 intermediate revisions not shown.)
Line 1: Line 1:
-
{{STRUCTURE_1zjd| PDB=1zjd | SCENE= }}
 
-
===Crystal Structure of the Catalytic Domain of Coagulation Factor XI in Complex with Kunitz Protease Inhibitor Domain of Protease Nexin II===
 
-
{{ABSTRACT_PUBMED_16085935}}
 
-
==Disease==
+
==Crystal Structure of the Catalytic Domain of Coagulation Factor XI in Complex with Kunitz Protease Inhibitor Domain of Protease Nexin II==
-
[[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> [[http://www.uniprot.org/uniprot/A4_HUMAN A4_HUMAN]] Defects in APP are the cause of Alzheimer disease type 1 (AD1) [MIM:[http://omim.org/entry/104300 104300]]. AD1 is a familial early-onset form of Alzheimer disease. It can be associated with cerebral amyloid angiopathy. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death.<ref>PMID:8476439</ref><ref>PMID:15201367</ref><ref>PMID:1671712</ref><ref>PMID:1908231</ref><ref>PMID:1678058</ref><ref>PMID:1944558</ref><ref>PMID:1925564</ref><ref>PMID:1415269</ref><ref>PMID:1303239</ref><ref>PMID:1302033</ref><ref>PMID:1303275</ref><ref>PMID:8267572</ref><ref>PMID:8290042</ref><ref>PMID:8577393</ref><ref>PMID:9328472</ref><ref>PMID:9754958</ref><ref>PMID:10097173</ref><ref>PMID:10631141</ref><ref>PMID:10665499</ref><ref>PMID:10867787</ref><ref>PMID:11063718</ref><ref>PMID:11311152</ref><ref>PMID:11528419</ref><ref>PMID:12034808</ref><ref>PMID:15365148</ref><ref>PMID:15668448</ref> Defects in APP are the cause of cerebral amyloid angiopathy APP-related (CAA-APP) [MIM:[http://omim.org/entry/605714 605714]]. A hereditary localized amyloidosis due to amyloid-beta A4 peptide(s) deposition in the cerebral vessels. The principal clinical characteristics are recurrent cerebral and cerebellar hemorrhages, recurrent strokes, cerebral ischemia, cerebral infarction, and progressive mental deterioration. Patients develop cerebral hemorrhage because of the severe cerebral amyloid angiopathy. Parenchymal amyloid deposits are rare and largely in the form of pre-amyloid lesions or diffuse plaque-like structures. They are Congo red negative and lack the dense amyloid cores commonly present in Alzheimer disease. Some affected individuals manifest progressive aphasic dementia, leukoencephalopathy, and occipital calcifications.<ref>PMID:10821838</ref><ref>PMID:2111584</ref><ref>PMID:11409420</ref><ref>PMID:12654973</ref><ref>PMID:16178030</ref>
+
<StructureSection load='1zjd' size='340' side='right'caption='[[1zjd]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[1zjd]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZJD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZJD 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]] 2.6&#8491;</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=1zjd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zjd OCA], [https://pdbe.org/1zjd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zjd RCSB], [https://www.ebi.ac.uk/pdbsum/1zjd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zjd 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/zj/1zjd_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=1zjd ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Factor XIa (FXIa) is a serine protease important for initiating the intrinsic pathway of blood coagulation. Protease nexin 2 (PN2) is a Kunitz-type protease inhibitor secreted by activated platelets and a physiologically important inhibitor of FXIa. Inhibition of FXIa by PN2 requires interactions between the two proteins that are confined to the catalytic domain of the enzyme and the Kunitz protease inhibitor (KPI) domain of PN2. Recombinant PN2KPI and a mutant form of the FXI catalytic domain (FXIac) were expressed in yeast, purified to homogeneity, co-crystallized, and the structure of the complex was solved at 2.6 angstroms (Protein Data Bank code 1ZJD). In this complex, PN2KPI has a characteristic, disulfide-stabilized double loop structure that fits into the FXIac active site. To determine the contributions of residues within PN2KPI to its inhibitory activity, selected point mutations in PN2KPI loop 1 11TGPCRAMISR20 and loop 2 34FYGGC38 were tested for their ability to inhibit FXIa. The P1 site mutation R15A completely abolished its ability to inhibit FXIa. IC50 values for the wild type protein and the remaining mutants were as follows: PN2KPI WT, 1.28 nM; P13A, 5.92 nM; M17A, 1.62 nM; S19A, 1.86 nM; R20A, 5.67 nM; F34A, 9.85 nM. The IC50 values for the M17A and S19A mutants were not significantly different from those obtained with wild type PN2KPI. These functional studies and activated partial thromboplastin time analysis validate predictions made from the PN2KPI-FXIac co-crystal structure and implicate PN2KPI residues, in descending order of importance, Arg15, Phe34, Pro13, and Arg20 in FXIa inhibition by PN2KPI.
-
==Function==
+
Structural and mutational analyses of the molecular interactions between the catalytic domain of factor XIa and the Kunitz protease inhibitor domain of protease nexin 2.,Navaneetham D, Jin L, Pandey P, Strickler JE, Babine RE, Abdel-Meguid SS, Walsh PN J Biol Chem. 2005 Oct 28;280(43):36165-75. Epub 2005 Aug 6. PMID:16085935<ref>PMID:16085935</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/A4_HUMAN A4_HUMAN]] Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1.<ref>PMID:9168929</ref><ref>PMID:11544248</ref><ref>PMID:11943163</ref><ref>PMID:19225519</ref><ref>PMID:19901339</ref> Beta-amyloid peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu(2+) and Fe(3+) to Cu(+) and Fe(2+), respectively. Beta-amyloid 42 is a more effective reductant than beta-amyloid 40. Beta-amyloid peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. Beta-APP42 may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with Also bind GPC1 in lipid rafts.<ref>PMID:9168929</ref><ref>PMID:11544248</ref><ref>PMID:11943163</ref><ref>PMID:19225519</ref><ref>PMID:19901339</ref> Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain (By similarity).<ref>PMID:9168929</ref><ref>PMID:11544248</ref><ref>PMID:11943163</ref><ref>PMID:19225519</ref><ref>PMID:19901339</ref> The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.<ref>PMID:9168929</ref><ref>PMID:11544248</ref><ref>PMID:11943163</ref><ref>PMID:19225519</ref><ref>PMID:19901339</ref> N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).<ref>PMID:9168929</ref><ref>PMID:11544248</ref><ref>PMID:11943163</ref><ref>PMID:19225519</ref><ref>PMID:19901339</ref>
+
-
==About this Structure==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[1zjd]] 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=1ZJD OCA].
+
</div>
 +
<div class="pdbe-citations 1zjd" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
-
*[[Factor XIa|Factor XIa]]
+
*[[Factor XIa 3D structures|Factor XIa 3D structures]]
-
 
+
== References ==
-
==Reference==
+
<references/>
-
<ref group="xtra">PMID:016085935</ref><references group="xtra"/><references/>
+
__TOC__
-
[[Category: Coagulation factor XIa]]
+
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Abdel-Meguid, S S.]]
+
[[Category: Large Structures]]
-
[[Category: Babine, R E.]]
+
[[Category: Abdel-Meguid SS]]
-
[[Category: Jin, L.]]
+
[[Category: Babine RE]]
-
[[Category: Navaneetham, D.]]
+
[[Category: Jin L]]
-
[[Category: Pandey, P.]]
+
[[Category: Navaneetham D]]
-
[[Category: Strickler, J E.]]
+
[[Category: Pandey P]]
-
[[Category: Walsh, P N.]]
+
[[Category: Strickler JE]]
-
[[Category: Blood clotting]]
+
[[Category: Walsh PN]]
-
[[Category: Coagulation factor xi]]
+
-
[[Category: Hydrolase]]
+
-
[[Category: Kunitz protease inhibitory domain]]
+
-
[[Category: Nexin ii]]
+

Current revision

Crystal Structure of the Catalytic Domain of Coagulation Factor XI in Complex with Kunitz Protease Inhibitor Domain of Protease Nexin II

PDB ID 1zjd

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/1zjd"
Personal tools