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- Title
Site-directed Mutagenesis of Human Brain GABA Transaminase: Lysine-357 Is Involved in Cofactor Binding at the Active Site.
- Authors
Dae Won Kim; Chang Sik Yoon; Won Sik Eum; Byung Ryong Lee; Jae Jin An; Sun Hwa Lee; Seung Ree Lee; Jee-Yin Ahn; Oh-Shin Kwon; Tae-Cheon Kang; Moo Ho Won; Sung-Woo Cho; Kil Soo Lee; Jinseu Park; Soo Young Choi
- Abstract
γ-Aminobutyrate transaminase (GABA-T), a key enzyme of the GABA shunt, converts the major inhibitory neurotransmitter, GABA, to succinic semialdehyde. Although GABA-T is a pivotal factor implicated in the pathogenesis of various neurological disorders, its function remains to be elucidated. In an effort to clarify the structural and functional roles of specific lysyl residue in human brain GABA-T, we constructed human brain GABA-T mutants, in which the lysyl residue at position 357 was mutated to various amino acids including asparagine (K357N). The purified mutant GABA-T enzymes displayed neither catalytic activity nor absorption bands at 330 and 415 nm that are characteristic of pyridoxal-5'-phosphate (PLP) covalently linked to the protein. The wild type apoenzyme reconstituted with exogenous PLP had catalytic activity, while the mutant apoenzymes did not. These results indicate that lysine 357 is essential for catalytic function, and is involved in binding PLP at the active site.
- Publication
Molecules & Cells (Springer Nature), 2004, Vol 18, Issue 3, p314
- ISSN
1016-8478
- Publication type
Article
- DOI
10.1016/s1016-8478(23)13118-9