Structure and activity of the axon guidance protein MICAL

被引：67

作者：

Nadella, M

Bianchet, MA

Gabelli, SB

Barrila, J

Amzel, LM ^{[1
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2005年 / 102卷 / 46期

关键词：

hydrogen peroxide; hydroxylase; monooxygenase; x-ray diffraction;

D O I：

10.1073/pnas.0504838102

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 MICALfd is an FAD-containing module structurally similar to aromatic hydroxylases and amine oxiclases. 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,K-NAPDH = 222 mu M; k(cat) = 77 sec(-1)), a molecule with known signaling properties. We propose that the H2O2 produced by this reaction may be one of the signaling molecules involved in axon guidance by MICAL.

引用

页码：16830 / 16835

页数：6

共 46 条

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