2c4c
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Semaphorins are extracellular cell guidance cues that govern cytoskeletal | + | 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== | ==About this Structure== | ||
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[[Category: Berrow, N.]] | [[Category: Berrow, N.]] | ||
[[Category: Harlos, K.]] | [[Category: Harlos, K.]] | ||
| - | [[Category: Jones, E | + | [[Category: Jones, E Y.]] |
| - | [[Category: Kolodkin, A | + | [[Category: Kolodkin, A L.]] |
| - | [[Category: Owens, R | + | [[Category: Owens, R J.]] |
| - | [[Category: Pasterkamp, R | + | [[Category: Pasterkamp, R J.]] |
[[Category: Siebold, C.]] | [[Category: Siebold, C.]] | ||
| - | [[Category: Stuart, D | + | [[Category: Stuart, D I.]] |
| - | [[Category: Terman, J | + | [[Category: Terman, J R.]] |
| - | [[Category: Walter, T | + | [[Category: Walter, T S.]] |
[[Category: CL]] | [[Category: CL]] | ||
[[Category: FAD]] | [[Category: FAD]] | ||
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[[Category: zinc]] | [[Category: zinc]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:44:44 2008'' |
Revision as of 14:44, 21 February 2008
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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 and 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
Page seeded by OCA on Thu Feb 21 16:44:44 2008
Categories: Mus musculus | Single protein | Berrow, N. | Harlos, K. | Jones, E Y. | Kolodkin, A L. | Owens, R J. | Pasterkamp, R J. | Siebold, C. | Stuart, D I. | Terman, J R. | Walter, T S. | CL | FAD | Coiled coil | Cytoskeleton | Fad | Flavoprotein | Lim domain | Metal-binding | Signaling protein | Transport | Zinc
