Lode Wyns

1H, 13C and 15N assignments of a camelid nanobody directed against human α-synuclein

Nanobodies are single chain antibodies that are uniquely produced in Camelidae, e.g. camels and llamas. They have the desirable features of small sizes (Mwxa0<xa014xa0kDa) and high affinities against antigens (Kdxa0~xa0nM), making them ideal as structural probes for biomedically relevant motifs both in vitro and in vivo. We have previously shown that nanobody binding to amyloidogenic human lysozyme variants can effectively inhibit their aggregation, the process that is at the origin of systemic amyloid disease. Here we report the NMR assignments of a new nanobody, termed NbSyn2, which recognises the C-terminus of the intrinsically disordered protein, human α-synuclein (aS), whose aberrant self-association is implicated in Parkinson’s disease.

Crystallization and crystal manipulation of a steric chaperone in complex with its lipase substrate.

Bacterial lipases that are secreted via the type II secretion pathway require a lipase-specific foldase in order to obtain their native and biologically active conformation in the periplasmic space. The lipase-foldase complex from Burkholderia glumae (319 and 333 residues, respectively) was crystallized in two crystal forms. One crystal form belongs to space group P3(1)21 (P3(2)21), with unit-cell parameters a = b = 122.3, c = 98.2 A. A procedure is presented which improved the diffraction of these crystals from approximately 5 to 2.95 A. For the second crystal form, which belonged to space group C2 with unit-cell parameters a = 183.0, b = 75.7, c = 116.6 A, X-ray data were collected to 1.85 A.

A comparative structural study on the steroids [1,2,5]oxadiazolo[3′,4′:3,4]-5α-pregn-16-en-20-one oxime (HS998), [1,2,5]oxadiazolo[3′,4′:3,4]-5α-pregn-16-en-20-one (HS974), and [1,2,5]oxadiazolo[3′,4′:3,4]-5β-pregn-16-en-20-one (HS973) by NMR, molecular modeling, and X-ray investigations

Abstract The molecular structure of the steroids [1,2,5]oxadiazolo[3′,4′:3,4]-5α-pregn-16-en-20-one oxime, [1,2,5]oxadiazolo[3′,4′:3,4]-5α-pregn-16-en-20-one and [1,2,5]oxadiazolo[3′,4′:3,4]-5β-pregn-16-en-20-one has been determined. The proton-proton distances in the solid state from previous crystallographic studies are compared with the corresponding distances from novel and previous solution NMR as well as from novel in vacuo modeling studies.