A close-packed planar 4-atom motif serves as a variable-pathway mechanistic switching device in enzymatic catalysis.
We have found a new kind of structural motif that appears to be highly conserved among the pyridine nucleotide-linked alpha-amino acid dehydrogenases. This feature is comprised of four atoms closely packed in a planar form. Two of the atoms are donated by the enzyme, one is provided by the substrate (or reactive intermediate), a bound water molecule constitutes the fourth. This tetrad, by virtue of its spatial connectivity, constitutes a two-dimensional machine in contrast to the one-dimensional charge-relay system commonly observed at enzyme active sites. As such, this new motif is capable of more complex behavior permitting a wide variety of possible bonding patterns. Modulation of these potentially variable patterns can lead to qualitative differences in mechanism between structurally similar enzymes, and, in the case of a given enzyme, may constitute the core of its catalytic machinery. We offer a conjecture as to how such a structure may participate in enzymatic catalysis.
Fisher
Harvey F
HF
Laboratory of Molecular Biochemistry, VA Medical Center, Kansas City, Missouri 64128, USA. hfisher@kumc.edu
Maniscalco
Steven J
SJ
D020816:Amino Acid Motifs; D002384:Catalysis; D020134:Catalytic Domain; D017124:Conserved Sequence; D003605:D-Amino-Acid Oxidase / Q000737:chemistry* / Q000378:metabolism*; D006860:Hydrogen Bonding; D007700:Kinetics; D008958:Models, Molecular; D011487:Protein Conformation; D014867:Water / Q000737:chemistry / Q000378:metabolism
D014867:Water; D003605:D-Amino-Acid Oxidase