2C4C

Crystal structure of the NADPH-treated monooxygenase domain of MICAL

Summary for 2C4C

• Entry DOI: 10.2210/pdb2c4c/pdb
• Related: 2BRA 2BRY
• Descriptor: NEDD9-INTERACTING PROTEIN WITH CALPONIN HOMOLOGY AND LIM DOMAINS, FLAVIN-ADENINE DINUCLEOTIDE, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: cytoskeleton, fad, flavoprotein, lim domain, metal-binding, signaling protein, transport
• Biological source: MUS MUSCULUS (MOUSE)
• Cellular location: Cytoplasm : Q8VDP3
• Total number of polymer chains: 2
• Total formula weight: 112116.84

Authors

Siebold, C.,Berrow, N.,Walter, T.S.,Harlos, K.,Owens, R.J.,Terman, J.R.,Stuart, D.I.,Kolodkin, A.L.,Pasterkamp, R.J.,Jones, E.Y. (deposition date: 2005-10-18, release date: 2005-10-26, Last modification date: 2024-05-08)

Primary citation

Siebold, C.,Berrow, N.,Walter, T.S.,Harlos, K.,Owens, R.J.,Stuart, D.I.,Terman, J.R.,Kolodkin, A.L.,Pasterkamp, R.J.,Jones, E.Y.
High-Resolution Structure of the Catalytic Region of Mical (Molecule Interacting with Casl), a Multidomain Flavoenzyme-Signaling Molecule.
Proc.Natl.Acad.Sci.USA, 102:16836-, 2005

PubMed Abstract: 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.

PubMed: 16275925
DOI: 10.1073/PNAS.0504997102

Experimental method

X-RAY DIFFRACTION (2.9 Å)