Crystal Structure of Nicotinic Acid Mononucleotide Adenylyltransferase from Staphyloccocus aureus: Structural Basis for NaAD Interaction in Functional Dimer

Mycobacterial Nicotinate Mononucleotide Adenylyltransferase

“…5) that has been reported to act as an arm to recognize the NaMN substrate or, more importantly, to bind the NaAD product. This loop, usually disordered in the apo form of bacterial NadDs, becomes ordered upon contact with the substrate or product (22,23,37,38). Because this loop was not fully resolved in our structure, which is not uncommon in NadD structure apo forms, and to better elucidate its mechanistic role, we carried out a full alanine-scanning mutagenesis of the partially conserved motif Pro-44 -Lys-47.…”

“…However, bacterial NadD enzymes have been less studied, and although the three-dimensional structures were reported for some bacterial pathogens (16,(22)(23)(24), it has not been reported for NadD from Mtb. Recently, we reported for the first time the successful expression, purification, and basic kinetic properties of MtNadD (17).…”

Nicotinamide/nicotinic acid mononucleotide adenylyltransferase, new insights into an ancient enzyme

“…Indeed, the structures of NMNAT from archaea [13][14][15], eubacteria [16][17][18][19][20][21], and eukarya [22][23][24][25] have been reported. Interestingly, the NMNAT enzymatic activity is also found in proteins endowed with dual functions, whereby the NAD biosynthetic activity is associated with a second function residing on a different domain in a chimeric protein.…”

“…The NMNAT a/b domain exhibits a topological organization closely resembling the widely described dinucleotidebinding domain also known as the ''Rossmann fold,'' and provides the essential structural determinants for substrate recognition and catalysis as well as for oligomeric assembly. The C-terminal small domain appears to play an important structural role in connecting NMNAT to a domain that bears a second function in the chimeric proteins NadR and SyNadM-Nudix [19,33] (Fig. 2), but no obvious general function can be envisaged for this small domain in other NMNATs, although in a few cases it has been shown to contribute to the stabilization of homooligomers [13,22,24].…”

“…Therefore, it could be argued that the NMN versus NaMN binding sites in enzymes from different sources should diverge and contain peculiar structural determinants for the recognition of either form of the substrate. However, although the structures of several NMNATs in complex with NMN, NaMN, NAD or NaAD [14][15][16][17][18][19][20][21][23][24][25] have been reported, no exhaustive and general answer can be provided to the question of which and to what extent conserved versus peculiar structural determinants contribute to pyridine mononucleotide binding and dictate NMN versus NaMN substrate selectivity in the different enzymes. Even though satisfactory explanations have been provided for specific enzymes, no conserved structural patterns responsible for pyridine mononucleotide selectivity have emerged from the wealth of available structural data.…”