Solution structure of PMP-C: A new fold in the group of small serine proteinase inhibitors

Georges Mer, Hélène Hietter, Christine Kellenberger, Martin Renatus, Bang Luu, Jean François Lefèvre

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

The solution structure and the disulfide pairings of a 36-residue proteinase inhibitor isolated from the insect Locusta migratoria have been determined using NMR spectroscopy and simulated annealing calculations. The peptide, termed PMP-C, was previously shown to inhibit bovine a-chymotrypsin as well as human leukocyte elastase, and was also found to block high-voltage-activated Ca2+ currents in rat sensory neurones. PMP-C has a prolate ellipsoid shape and adopts a tertiary fold hitherto unobserved in the large group of small 'canonical' proteinase inhibitors. The over-all fold consists mainly of three strands arranged in a right-handed twisted, antiparallel, β-sheet that demarcates a cavity, together with a linear amino-terminal segment oriented almost perpendicular to the three strands of the β-sheet. Inside the cavity a phenyl ring constitutes the centre of a hydrophobic core. The proteinase binding loop is located in the carboxy-terminal part of the molecule, between two cysteine residues involved in disulfide bridges. Its conformation resembles that found in other small canonical proteinase inhibitors. A comparison of PMP-C structure with the recently published solution structure of the related peptide PMP-D2 shows that the most significant differences are complementary changes involved in the stabilization of similar folds. This comparison led us to review the structure of PMP-D2 and to identify two salt bridges in PMP-D2

Original languageEnglish (US)
Pages (from-to)158-171
Number of pages14
JournalJournal of Molecular Biology
Volume258
Issue number1
DOIs
StatePublished - Apr 26 1996

Keywords

  • Calcium channel blocker
  • Disulfide bridge
  • Locusta migratoria
  • NMR
  • Proteinase inhibitor

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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