Insights into ligand binding and catalysis of a central step in NAD(+) synthesis - Structures of Methanobacterium thermoautotrophicum NMN adenylyltransferase complexes
V. Saridakis et al., Insights into ligand binding and catalysis of a central step in NAD(+) synthesis - Structures of Methanobacterium thermoautotrophicum NMN adenylyltransferase complexes, J BIOL CHEM, 276(10), 2001, pp. 7225-7232
Nicotinamide mononucleotide adenylyltransferase (NMNATase) catalyzes the li
nking of NMN+ or NaMN+ with ATP, which in all organisms is one of the commo
n step in the synthesis of the ubiquitous coenzyme NAD(+) via both de novo
and salvage biosynthetic pathways. The structure of Methanobacterium thermo
autotrophicum NMNATase determined using multiwavelength anomalous dispersio
n phasing revealed a nucleotide-binding fold common to nucleotidyltransfera
se proteins. An NAD+ molecule and a sulfate ion were bound in the active si
te allowing the identification of residues involved in product binding. In
addition, the role of the conserved (16)HXGH(19) active site motif in catal
ysis was probed by mutagenic, enzymatic and crystallographic techniques, in
cluding the characterization of an NMN+/SO42- complex of mutant H19A NMNATa
se.