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- Title
Structure of P-protein of the glycine cleavage system: implications for nonketotic hyperglycinemia.
- Authors
Nakai, Tadashi; Nakagawa, Noriko; Maoka, Nobuko; Masui, Ryoji; Kuramitsu, Seiki; Kamiya, Nobuo
- Abstract
The crystal structure of the P-protein of the glycine cleavage system from Thermus thermophilus HB8 has been determined. This is the first reported crystal structure of a P-protein, and it reveals that P-proteins do not involve theα2-type active dimer universally observed in the evolutionarily related pyridoxal 5′-phosphate (PLP)-dependent enzymes. Instead, novelαβ-type dimers associate to form anα2β2 tetramer, where theα- andβ-subunits are structurally similar and appear to have arisen by gene duplication and subsequent divergence with a loss of one active site. The binding of PLP to the apoenzyme induces large open–closed conformational changes, with residues moving up to 13.5Å. The structure of the complex formed by the holoenzyme bound to an inhibitor, (aminooxy)acetate, suggests residues that may be responsible for substrate recognition. The molecular surface around the lipoamide-binding channel shows conservation of positively charged residues, which are possibly involved in complex formation with the H-protein. These results provide insights into the molecular basis of nonketotic hyperglycinemia.
- Subjects
PROTEINS; GLYCINE; ENZYMES; BINDING sites; BIOCHEMISTRY; ACETATES
- Publication
EMBO Journal, 2005, Vol 24, Issue 8, p1523
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1038/sj.emboj.7600632