Dihydroneopterin aldolase (DHNA) catalyzes the conversion of the 7,8-dihydroneopterin (DHNP) to 6-hydroxymethyl-7,8-dihydropterin (HP) in the folate biosynthetic pathway, one of principal targets for developing antimicrobial agents. Folate cofactors are essential for life. Most microorganisms must synthesize folates de novo. In contrast, mammals cannot synthesize folates because of the lack of three enzymes in the middle of the folate pathway and obtain folates from the diet. DHNA is the first of the three enzymes that are absent in mammals and therefore an attractive target for developing antimicrobial agents. DHNA is a unique aldolase in two respects. First, DHNA requires neither the formation of a Schiff base between the substrate and enzyme nor metal ions for catalysis . Aldolases can be divided into two classes based on their catalytic mechanisms. Class I aldolases require the formation of a Schiff base between an amino group of the enzyme and the carbonyl of the substrate, whereas class II aldolases require a Zn2+ ion at their active sites for catalysis. The proposed catalytic mechanism for DHNA is similar to that of class I aldolases, but the Schiff base is embedded in the substrate. Secondly, in addition to the aldolase reaction, DHNA also catalyzes the epimerization at the 2′-carbon of DHNP to generate 7,8-dihydromonapterin (DHMP). Here you can see the crystal structure of Dihydroneopterin aldolase from Yersinia pestis (PDB code: 7SU6)
#molecularart ... #immolecular ... #Dihydroneopterin .. #aldolase ... #multimer ... #antibiotic ... #yersinia ... #xray
Structure rendered with @proteinimaging and depicted with @corelphotopaint
#molecularart ... #immolecular ... #Dihydroneopterin .. #aldolase ... #multimer ... #antibiotic ... #yersinia ... #xray
Structure rendered with @proteinimaging and depicted with @corelphotopaint
