TY - JOUR
T1 - Solution structure of PMP-C
T2 - A new fold in the group of small serine proteinase inhibitors
AU - Mer, Georges
AU - Hietter, Hélène
AU - Kellenberger, Christine
AU - Renatus, Martin
AU - Luu, Bang
AU - Lefèvre, Jean François
PY - 1996/4/26
Y1 - 1996/4/26
N2 - 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
AB - 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
KW - Calcium channel blocker
KW - Disulfide bridge
KW - Locusta migratoria
KW - NMR
KW - Proteinase inhibitor
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U2 - 10.1006/jmbi.1996.0240
DO - 10.1006/jmbi.1996.0240
M3 - Article
C2 - 8613985
AN - SCOPUS:0030004582
SN - 0022-2836
VL - 258
SP - 158
EP - 171
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 1
ER -