In biotechnology and drug delivery silica materials are of interest but the controlled generation of silicic acid is difficult. To get more insight into the molecular mechanisms that control biosilification, it is important to study the proteins involved in this process. The sponge protein silicatein α synthesises part of the axial filament in the spicules which in situ polymerises silicic acid. It has been demonstrated that the polymerisation of siloxanes such as for example tetraethoxysilane (TEOS) can be carried out by both wild type and recombinant silicatein α. Unfortunately, it has not been possible yet to get reasonable amounts of wild type or recombinant silicatein α to perform biophysical studies. The human cysteine protease cathepsin L has almost 50 % identical residues with silicatein α. To get more insight into the mechanism of silica polymerisation, cathepsin L mutants were generated by our collaborators. Those mutants show sequence features and activity specific for silicatein α. The X-ray structure of one of those mutants (mutant 4SER) to 1.5 Å has allowed us to propose a new chemical mechanism for the catalysis of silicic acid polymerisation. ADP-β-D-glycero-D-mannoheptose and ADP-β-L-glycero-D-mannoheptose are interconverted by the SDR-enzyme ADP-β-L-glycero-D-mannoheptose 6-epimerase (AGME). This epimerisation reaction is the final reaction in the biosynthetic route of the precursor of heptose. Heptose is a part of the inner core of the lipopolysaccharide in Gram-negative bacteria. In mutants which do not have heptose, nonpolar compounds can penetrate more easily through the outer membrane. These mutants also show less pathogenicity. As a consequence the lipopolysaccharide biosynthetic pathway represents an interesting target for antimicrobial compounds. The crystal structure of AGME in complex with ADP-α-glucose has already been solved. From this structure a catalytic mechanism for this enzyme has been proposed with Tyr140 and Lys178 operating as acid/base residues. The disordered nature of the nucleotide sugar’s glucose moiety in the previous structure due to the wrong configuration of the sugar has hindered assignment of a mechanism. The determination of the X-ray structure of AGME Y140F in complex with a substrate in the β-manno configuration (ADP-β-mannose) to 2.4 Å resolution has given new insight into the mechanism of this SDR enzyme. A mechanism is proposed with only Tyr140 operating as catalytic acid/base. Initially it was thought that MMP-3 participates in the synovitis cascade. Glycoproteins, several parts of the ECM such as fibronectin and laminin and also collagens and procollagens are targets of this matrixin. Furthermore MMP-3 can undergo autocatalysis and is also able to cleave a range of other members of the matrixin family. Matrixins also play an important role in diseases such as cancer, rheumatoid arthritis and osteoporosis. This makes them targets for inhibitor design. Many structures of matrix metalloproteinases, such as stromelysin-1, in complex with various inhibitors have already been solved. The structures of the catalytic domain of MMP-3 in complex with two nonpeptide inhibitors are discussed.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 4 uppsatser.

Lic.-avh. (sammanfattning) Umeå : University. / Härtill 3 uppsatser.

Thesis (M.D.)--University of Adelaide, Dept. of Surgery, 2002. / Includes bibliographical references (leaves 292-352).

Thesis (Ph. D.)--University of Hong Kong, 2008. / Includes bibliographical references (leaf 153-171) Also available in print.

Thesis (Ph. D.)--University of Missouri--Columbia, 2004. / Typescript. Vita. Includes bibliographical references (leaves 104-115). Also issued on the Internet.

Thesis (M.S.)--University of Missouri--Columbia, 2003. / "December 2003." Typescript. Includes bibliographical references (leaves 76-90). Also issued on the Internet.

Thesis (Ph. D.)--University of Missouri--Columbia, 2004. / "July 2004." Typescript. Vita. Includes bibliographical references (leaves 104-115). Also issued on the Internet.

Thesis (M.Sc.)--University of Alberta, 2010. / A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Master of Science in Physiology. Title from pdf file main screen (viewed on February 16, 2010). Includes bibliographical references.

Thesis (M.S.)--University of Missouri-Columbia, 2006. / "December 2006" The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Includes bibliographical references.