Solution structure of PMP-C: a new fold in the group of small serine proteinase inhibitors.
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 alpha-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, beta-sheet that demarcates a cavity, together with a linear amino-terminal segment oriented almost perpendicular to the three strands of the beta-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.
Mer
G
G
CNRS-UPR 9003, Ecole Supérieure de Biotechnologie de Strasbourg, Illkirch-Graffenstaden, France.
Hietter
H
H
Kellenberger
C
C
Renatus
M
M
Luu
B
B
Lefèvre
J F
JF
D000595:Amino Acid Sequence; D000818:Animals; D047169:Cyclotides; D004220:Disulfides / Q000737:chemistry; D006110:Grasshoppers / Q000737:chemistry; D007301:Insect Hormones / Q000737:chemistry*; D019476:Insect Proteins; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D015842:Serine Proteinase Inhibitors / Q000737:chemistry*
D047169:Cyclotides; D004220:Disulfides; D007301:Insect Hormones; D019476:Insect Proteins; D015842:Serine Proteinase Inhibitors; C072986:PMP-D2 peptide, insect; C072987:PMP-C peptide, insect