View source for 9blj


==Crystal structure of a serine protease inhibitor HPI from Hevea brasiliensis==
<StructureSection load='9blj' size='340' side='right'caption='[[9blj]], [[Resolution|resolution]] 1.74&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9blj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Hevea_brasiliensis Hevea brasiliensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9BLJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9BLJ 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]] 1.74&#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=9blj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9blj OCA], [https://pdbe.org/9blj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9blj RCSB], [https://www.ebi.ac.uk/pdbsum/9blj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9blj ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HPI_HEVBR HPI_HEVBR] Inhibitor of serine proteases, strongly inhibits subtilisin A and weakly inhibits trypsin. Does not inhibit chymotrypsin, papain, pepsin, pronase E, protease type XIII and thermolysin. HPI-1 inhibits subtilisin A with an Ki of 0.21 nM. HPI-2a inhibits subtilisin A with an Ki of 0.08 nM. HPI-2b inhibits subtilisin A with an Ki of 0.1 nM.<ref>PMID:16438995</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Protease inhibitors are crucial in regulating enzymatic activity and have extensive applications in medicine, biotechnology, and agriculture. This study characterizes a recombinant protease inhibitor from Hevea brasiliensis (rHPI), highlighting its unique structural features and inhibitory potential. Using Matrix-Assisted Laser Desorption/Ionization (MALDI) analysis, the inhibitor exhibits one distinct peak around 7.54 kDa. Enzymatic assays using N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide as a substrate confirmed the inhibitor's activity against subtilisin Carlsberg, a widely utilized serine protease in industry and biotechnology. The crystal structure of rHPI, resolved at 1.73 A, reveals a topology closely resembling eglin c, including a single alpha-helix, two parallel beta-strands, and a distinctive binding loop spanning residues 40-51. Disordered regions at the N- and C-termini contribute to its structural uniqueness. Despite lacking disulfide bonds and featuring an Arg residue instead of Trp at the P'(8) position, rHPI maintains a high affinity for subtilisin. Isothermal titration calorimetry (ITC) showed that this interaction is entropically driven. Molecular docking and dynamics simulations of the rHPI-subtilisin complex revealed the formation of antiparallel beta-sheets, hydrogen bonding involving the protein backbone, and a salt bridge between His64 of subtilisin and Asp47 of rHPI. These findings provide valuable insights into the molecular basis of rHPI's inhibitory activity and offer a framework for the rational design of novel subtilisin inhibitors with potential applications in agricultural and industrial settings.

Understanding the structure and function of HPI, a rubber tree serine protease inhibitor, and its interaction with subtilisin.,Terron-Hernandez J, Gomez-Velasco H, Pinzon-Yaya L, Hernandez-Santoyo A, Garcia-Ramirez B, Rodriguez-Romero A Biochem Biophys Res Commun. 2025 May 12;763:151801. doi: , 10.1016/j.bbrc.2025.151801. Epub 2025 Apr 11. PMID:40233429<ref>PMID:40233429</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9blj" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Hevea brasiliensis]]
[[Category: Large Structures]]
[[Category: Hernandez-Santoyo A]]
[[Category: Rodriguez-Romero A]]