View source for 8hwu


==Solution structure of frog peptide LL-TIL==
<StructureSection load='8hwu' size='340' side='right'caption='[[8hwu]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8hwu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lepidobatrachus_laevis Lepidobatrachus laevis]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8HWU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HWU FirstGlance]. <br>
</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=8hwu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hwu OCA], [https://pdbe.org/8hwu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8hwu RCSB], [https://www.ebi.ac.uk/pdbsum/8hwu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8hwu ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Subtilases play a significant role in microbial pathogen infections by degrading the host proteins. Subtilisin inhibitors are crucial in fighting against these harmful microorganisms. LL-TIL, from skin secretions of Lepidobatrachus laevis, is a cysteine-rich peptide belonging to the I8 family of inhibitors. Protease inhibitory assays demonstrated that LL-TIL acts as a slow-tight binding inhibitor of subtilisin Carlsberg and proteinase K with inhibition constants of 91 pM and 2.4 nM, respectively. The solution structures of LL-TIL and a mutant peptide reveal that they adopt a typical TIL-type fold with a canonical conformation of a reactive site loop (RSL). The structure of the LL-TIL-subtilisin complex and molecular dynamics (MD) simulations provided an in-depth view of the structural basis of inhibition. NMR relaxation data and molecular dynamics simulations indicated a rigid conformation of RSL, which does not alter significantly upon subtilisin binding. The energy calculation for subtilisin inhibition predicted Ile(31) as the highest contributor to the binding energy, which was confirmed experimentally by site-directed mutagenesis. A chimeric mutant of LL-TIL broadened the inhibitory profile and attenuated subtilisin inhibition by 2 orders of magnitude. These results provide a template to engineer more specific and potent TIL-type subtilisin inhibitors.

Structural, Functional, and Mutational Studies of a Potent Subtilisin Inhibitor from Budgett's Frog, Lepidobatrachus laevis.,Rami M, Shafique M, Sarma SP Biochemistry. 2023 Oct 17;62(20):2952-2969. doi: 10.1021/acs.biochem.3c00252. , Epub 2023 Oct 5. PMID:37796763<ref>PMID:37796763</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Lepidobatrachus laevis]]
[[Category: Rami MJ]]
[[Category: Sarma SP]]