The solution structure and dynamics of human neutrophil gelatinase-associated lipocalin Coles, M Diercks, T Muehlenweg, B Bartsch, S Zolzer, V Tschesche, Harald Kessler, H protein structure NMR human neutrophil gelatinase-associated lipocalin protein-protein interactions protein dynamics Human neutrophil gelatinase-associated lipocalin (HNGAL) is a member of the lipocalin family of extracellular proteins that function as transporters of small, hydrophobic molecules. HNGAL, a component of human blood granulocytes, binds bacterially derived formyl peptides that act as chemotactic agents and induce leukocyte granule discharge. HNGAL also forms a complex with the proenzyme form of matrix metalloproteinase-9 (pro-MMP-9, or progelatinase B) via an intermolecular disulphide bridge. This association allows the subsequent formation of ternary and quaternary metalloproteinase/inhibitor complexes that vary greatly in their metalloproteinase activities. The structure and dynamics of apo-HNGAL have been determined by NMR spectroscopy. Simulated annealing calculations yielded a set of 20 convergent structures with an average backbone RMSD from mean coordinate positions of 0.79(+/-0.13) Angstrom over secondary structure elements. The overall rotational correlation time (13.3 ns) derived from N-15 relaxation data is consistent with a monomeric protein of the size of HNGAL (179 residues) under the experimental conditions (1.4 mM protein, pH 6.0, 24.5 degrees C). The structure features an eight stranded antiparallel beta-barrel, typical of the lipocalin family. One end of the barrel is open, providing access to the binding site within the barrel cavity, while the other is closed by a short 3(10)-helix. The free cysteine residue required for association with pro-MMP-9 lies in an inter-strand loop at the closed end of the barrel. The structure provides a detailed model of the ligand-binding site and has led to the proposal of a site for pro-MMP-9 association. Dynamic data correlate well with structural features, which has allowed us to investigate a mechanism by which a cell-surface receptor might distinguish between apo and holo-HNGAL through conformational changes at the open end of the barrel. (C) 1999 Academic Press. ACADEMIC PRESS LTD 1999 info:eu-repo/semantics/article doc-type:article text Coles M, Diercks T, Muehlenweg B, et al. The solution structure and dynamics of human neutrophil gelatinase-associated lipocalin. <em>JOURNAL OF MOLECULAR BIOLOGY</em>. 1999;289(1):139-157. eng info:eu-repo/semantics/altIdentifier/doi/10.1006/jmbi.1999.2755 info:eu-repo/semantics/altIdentifier/issn/0022-2836 info:eu-repo/semantics/altIdentifier/wos/000080818700013 info:eu-repo/semantics/altIdentifier/pmid/10339412 info:eu-repo/semantics/closedAccess