3l33: Difference between revisions
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< | ==Human mesotrypsin complexed with amyloid precursor protein inhibitor(APPI)== | ||
<StructureSection load='3l33' size='340' side='right'caption='[[3l33]], [[Resolution|resolution]] 2.48Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3l33]] is a 8 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=3L33 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3L33 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]] 2.48Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</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=3l33 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l33 OCA], [https://pdbe.org/3l33 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3l33 RCSB], [https://www.ebi.ac.uk/pdbsum/3l33 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3l33 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/TRY3_HUMAN TRY3_HUMAN] Digestive protease specialized for the degradation of trypsin inhibitors. In the ileum, may be involved in defensin processing, including DEFA5.<ref>PMID:12021776</ref> <ref>PMID:14507909</ref> | |||
== 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/l3/3l33_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=3l33 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
An important functional property of protein protease inhibitors is their stability to proteolysis. Mesotrypsin is a human trypsin that has been implicated in the proteolytic inactivation of several protein protease inhibitors. We have found that bovine pancreatic trypsin inhibitor (BPTI), a Kunitz protease inhibitor, inhibits mesotrypsin very weakly and is slowly proteolyzed, whereas, despite close sequence and structural homology, the Kunitz protease inhibitor domain of the amyloid precursor protein (APPI) binds to mesotrypsin 100 times more tightly and is cleaved 300 times more rapidly. To define features responsible for these differences, we have assessed the binding and cleavage by mesotrypsin of APPI and BPTI reciprocally mutated at two nonidentical residues that make direct contact with the enzyme. We find that Arg at P(1) (versus Lys) favors both tighter binding and more rapid cleavage, whereas Met (versus Arg) at P'(2) favors tighter binding but has minimal effect on cleavage. Surprisingly, we find that the APPI scaffold greatly enhances proteolytic cleavage rates, independently of the binding loop. We draw thermodynamic additivity cycles analyzing the interdependence of P(1) and P'(2) substitutions and scaffold differences, finding multiple instances in which the contributions of these features are nonadditive. We also report the crystal structure of the mesotrypsin.APPI complex, in which we find that the binding loop of APPI displays evidence of increased mobility compared with BPTI. Our data suggest that the enhanced vulnerability of APPI to mesotrypsin cleavage may derive from sequence differences in the scaffold that propagate increased flexibility and mobility to the binding loop. | |||
Determinants of affinity and proteolytic stability in interactions of Kunitz family protease inhibitors with mesotrypsin.,Salameh MA, Soares AS, Navaneetham D, Sinha D, Walsh PN, Radisky ES J Biol Chem. 2010 Nov 19;285(47):36884-96. Epub 2010 Sep 22. PMID:20861008<ref>PMID:20861008</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3l33" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Amyloid precursor protein 3D structures|Amyloid precursor protein 3D structures]] | |||
*[[Trypsin 3D structures|Trypsin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Radisky | [[Category: Radisky ES]] | ||
[[Category: Salameh | [[Category: Salameh MA]] | ||
[[Category: Soares | [[Category: Soares AS]] | ||