2c4c

From Proteopedia

Revision as of 16:59, 18 December 2007

CRYSTAL STRUCTURE OF THE NADPH-TREATED MONOOXYGENASE DOMAIN OF MICAL

Overview

Semaphorins are extracellular cell guidance cues that govern cytoskeletal, dynamics during neuronal and vascular development. MICAL (molecule, interacting with CasL) is a multidomain cytosolic protein with a putative, flavoprotein monooxygenase (MO) region required for semaphorin-plexin, repulsive axon guidance. Here, we report the 1.45-A resolution crystal, structure of the FAD-containing MO domain of mouse MICAL-1 (residues, 1-489). The topology most closely resembles that of the NADPH-dependent, flavoenzyme p-hydroxybenzoate hydroxylase (PHBH). Comparison of structures, before and after reaction with NADPH reveals that, as in PHBH, the flavin, ring can switch between two discrete positions. In contrast with other, MOs, this conformational switch is coupled with the opening of a channel, to the active site, suggestive of a protein substrate. In support of this, hypothesis, distinctive structural features highlight putative, protein-binding sites in suitable proximity to the active site entrance., The unusual juxtaposition of this N-terminal MO (hydroxylase) activity, with the characteristics of a multiprotein-binding scaffold exhibited by, the C-terminal portion of the MICALs represents a unique combination of, functionality to mediate signaling.

About this Structure

2C4C is a Single protein structure of sequence from Mus musculus with CL and FAD as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

High-resolution structure of the catalytic region of MICAL (molecule interacting with CasL), a multidomain flavoenzyme-signaling molecule., Siebold C, Berrow N, Walter TS, Harlos K, Owens RJ, Stuart DI, Terman JR, Kolodkin AL, Pasterkamp RJ, Jones EY, Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16836-41. Epub 2005 Nov 7. PMID:16275925

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