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Publication : Structure and activity of the axon guidance protein MICAL.

First Author  Nadella M Year  2005
Journal  Proc Natl Acad Sci U S A Volume  102
Issue  46 Pages  16830-5
PubMed ID  16275926 Mgi Jnum  J:103740
Mgi Id  MGI:3610674 Doi  10.1073/pnas.0504838102
Citation  Nadella M, et al. (2005) Structure and activity of the axon guidance protein MICAL. Proc Natl Acad Sci U S A 102(46):16830-5
abstractText  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 A resolution. The structure shows that MICAL(fd) is an FAD-containing module structurally similar to aromatic hydroxylases and amine oxidases. In addition, we present biochemical data that show that MICAL(fd) is a flavoenzyme that in the presence of NADPH reduces molecular oxygen to H(2)O(2) (K(m,NAPDH) = 222 microM; k(cat) = 77 sec(-1)), a molecule with known signaling properties. We propose that the H(2)O(2) produced by this reaction may be one of the signaling molecules involved in axon guidance by MICAL.
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