L-Aminoacid oxidase, biochemical mechanism and apoptose induction

Description

L-amino acid oxidase (LAAO) is a classical flavoenzyme that was discovered some 60 years ago in snake venom. It is glycosylated and is characterized by several interesting biological features such as bactericidal and apoptosis-inducing properties. The molecular mechanism of the latter are still unclear. We have elucidated the three-dimensional structure of the LAAO from Calloselasma rhodostoma and the structure of its N-glycan substituents. Remarkably, at the active center no functional groups appear to be present that might play a direct role in substrate dehydrogenation, a acids that are known to mediate cell surface recognition phenomena. Recently the hypothesis has been put forward, that induction of apoptosis by LAAO involves a specific interaction with the cell surface in addition to the well-known toxic effects of H2O2 towards cells and tissue. This proposal is questionable and requires verification. The 3D-structure is characterized by the presence of a long channel leading to the active center. One saccharide substituent is located at the outlet of teh channel and it could thus mediate a regiospecific interaction with the cell surface thereby inducing a high local H2O2 concentration. The project shall contribute to the elucidation of the dehydrogenation mechanism by LAAO and verify the mentioned hypothesis concerning apoptosis induction.

Institutions
  • FB Biologie
Funding sources
Name Project no. Description Period
Deutsche Forschungsgemeinschaft553/02no information
Further information
Period: 01.03.2002 – 28.02.2004