2kmo: Difference between revisions
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==Solution structure of native Leech-derived tryptase inhibitor, LDTI== | ==Solution structure of native Leech-derived tryptase inhibitor, LDTI== | ||
<StructureSection load='2kmo' size='340' side='right'caption='[[2kmo | <StructureSection load='2kmo' size='340' side='right'caption='[[2kmo]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2kmo]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[2kmo]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KMO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KMO FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</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=2kmo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kmo OCA], [https://pdbe.org/2kmo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kmo RCSB], [https://www.ebi.ac.uk/pdbsum/2kmo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kmo ProSAT]</span></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=2kmo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kmo OCA], [https://pdbe.org/2kmo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kmo RCSB], [https://www.ebi.ac.uk/pdbsum/2kmo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kmo ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/LDTI_HIRME LDTI_HIRME] Acts as an inhibitor of human tryptase, trypsin and chymotrypsin. Probably acts to block host defense mechanisms. | |||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/km/2kmo_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/km/2kmo_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/ | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </jmolCheckbox> | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Hirudo medicinalis]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Pantoja-Uceda | [[Category: Pantoja-Uceda D]] | ||
[[Category: Santoro | [[Category: Santoro J]] | ||
Latest revision as of 12:15, 6 November 2024
Solution structure of native Leech-derived tryptase inhibitor, LDTISolution structure of native Leech-derived tryptase inhibitor, LDTI
Structural highlights
FunctionLDTI_HIRME Acts as an inhibitor of human tryptase, trypsin and chymotrypsin. Probably acts to block host defense mechanisms. 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 PubMedProtein folding mechanisms have remained elusive mainly because of the transient nature of intermediates. Leech-derived tryptase inhibitor (LDTI) is a Kazal-type serine proteinase inhibitor that is emerging as an attractive model for folding studies. It comprises 46 amino acid residues with three disulfide bonds, with one located inside a small triple-stranded antiparallel beta-sheet and with two involved in a cystine-stabilized alpha-helix, a motif that is widely distributed in bioactive peptides. Here, we analyzed the oxidative folding and reductive unfolding of LDTI by chromatographic and disulfide analyses of acid-trapped intermediates. It folds and unfolds, respectively, via sequential oxidation and reduction of the cysteine residues that give rise to a few 1- and 2-disulfide intermediates. Species containing two native disulfide bonds predominate during LDTI folding (IIa and IIc) and unfolding (IIa and IIb). Stop/go folding experiments demonstrate that only intermediate IIa is productive and oxidizes directly into the native form. The NMR structures of acid-trapped and further isolated IIa, IIb, and IIc reveal global folds similar to that of the native protein, including a native-like canonical inhibitory loop. Enzyme kinetics shows that both IIa and IIc are inhibitory-active, which may substantially reduce proteolysis of LDTI during its folding process. The results reported show that the kinetics of the folding reaction is modulated by the specific structural properties of the intermediates and together provide insights into the interdependence of conformational folding and the assembly of native disulfides during oxidative folding. Deciphering the structural basis that guides the oxidative folding of leech-derived tryptase inhibitor.,Pantoja-Uceda D, Arolas JL, Aviles FX, Santoro J, Ventura S, Sommerhoff CP J Biol Chem. 2009 Dec 18;284(51):35612-20. Epub . PMID:19820233[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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