Structural basis for the inactivation of AdoMetDC K12R mutant.
S-adenosylmethionine decarboxylase (AdoMetDC) is a key enzyme in the biosynthesis of the polyamines spermidine and spermine. Polyamines are ubiquitous organic cations that are absolutely required for normal cell proliferation and differentiation. AdoMetDC catalyzes decarboxylation of S-adenosylmethionine (AdoMet) which provides aminopropyl groups for spermidine and spermine synthesis. Mammalian AdoMetDC is produced as a proenzyme (38 kDa) which is cleaved to form the alpha (30.7 kDa) and beta (7.7 kDa) subunits of the mature enzyme. It is here shown that the catalytic activity of the enzyme was completely eliminated when lysine 12 was mutated to an arginine residue in the small subunit; however, the proenzyme processing was not affected. On the other hand, mutations of other lysine residues (Lys45-->Arg and Lys56-->Arg) did not affect either the enzyme activity or the proenzyme processing. Structure analysis using Swiss Deep Viewer v3.7 has indicated that Arg in place of Lys12 may eliminate AdoMetDC activity by restricting the mobility of Thr85 through hydrogen bonding. Sequence alignment of various AdoMetDC sequences indicated that Thr85 is in a highly conserved region, suggesting that Thr85 is critical for the decarboxylation reaction.
Yerlikaya
Azmi
A
Dumlupinar University, Art and Science Faculty, Department of Biology, Kütahya, Turkey. azmiyerlikaya@hotmail.com
Stanley
Bruce A
BA
D012437:Adenosylmethionine Decarboxylase / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001120:Arginine / Q000378:metabolism; D015153:Blotting, Western; D019556:COS Cells; D002384:Catalysis; D002522:Chlorocebus aethiops; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D013912:Threonine / Q000737:chemistry
D013912:Threonine; D001120:Arginine; D012437:Adenosylmethionine Decarboxylase