Abstract
During development, neurons are guided to their targets by short- and long-range attractive and repulsive cues. MICAL, a large multidomain protein, is required for the combined action of semaphorins and plexins in axon guidance. Here, we present the structure of the N-terminal region of MICAL (MICAL fd) determined by x-ray diffraction to 2.0 Å resolution. The structure shows that MICALfd is an FAD-containing module structurally similar to aromatic hydroxylases and amine oxidases. In addition, we present biochemical data that show that MICALfd is a flavoenzyme that in the presence of NADPH reduces molecular oxygen to H2O2 (K m,NAPDH = 222 μM; kcat = 77 sec-1), a molecule with known signaling properties. We propose that the H 2O2 produced by this reaction may be one of the signaling molecules involved in axon guidance by MICAL.
Original language | English (US) |
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Pages (from-to) | 16830-16835 |
Number of pages | 6 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 102 |
Issue number | 46 |
DOIs | |
State | Published - Nov 15 2005 |
Externally published | Yes |
Keywords
- Hydrogen peroxide
- Hydroxylase
- Monooxygenase
- X-ray diffraction
ASJC Scopus subject areas
- General