Phosphodiesterase with HD-GYP domain (HD-GYP phosphodiesterase)

Phosphodiesterases with HD-GYP domains are bacterial enzymes belonging to the HD domain superfamily, uniquely equipped to hydrolyze cyclic di-GMP (bis-(3',5')-cyclic dimeric guanosine monophosphate)—a key bacterial second messenger controlling cellular processes such as biofilm formation, motility, and virulence[1][3][4]. HD-GYP phosphodiesterases contain conserved motifs (HD and GYP) that coordinate transition metal ions (commonly Fe) in their active site, essential for catalysis[4][6]. They frequently act in opposition to diguanylate cyclases (GGDEF domain proteins) to fine-tune cyclic dinucleotide levels[1]. By modulating signal transduction pathways, these enzymes critically affect bacterial adaptation and pathogenicity, making them candidate targets for anti-biofilm and antimicrobial drug design[2]. No clinically approved drugs yet target these enzymes, but mechanistic knowledge underpins current efforts in therapeutic inhibitor development[2].

Other names

HD-GYP proteinHD-GYP domain phosphodiesterasec-di-GMP phosphodiesterase (HD-GYP type)

Hydrolysis of cyclic di-GMP or related cyclic dinucleotides, converting them into linear di-nucleotides or mononucleotides Modulation of bacterial secondary messenger levels, thereby altering bacterial physiology and pathogenicity[1][4].