Structure and Function of HD-GYP Phosphodiesterases

Abstract

HD-GYPs represent the least abundant, and somewhat mysterious, class of dedicated cyclic di-GMP phosphodiesterases (PDE). They are metal dependent enzymes, belonging to the HD phosphohydrolase superfamily, and are evolutionarily unrelated to the EAL class of cyclic di-GMP dedicated PDEs. In contrast to the EAL domain that hydrolyses cyclic di-GMP to pGpG, HD-GYPs are able to further hydrolyse pGpG to GMP. As both the GGDEF and EAL domains, the HD-GYP module is often found fused with other regulatory domains. Despite the ability to act as a PDE, the physiological role(s) of HD-GYP proteins within the cyclic di-GMP-dependent biofilm regulation are still not fully clarified. Indeed, many HD-GYPs may also mediate protein−protein interactions within more complex regulatory pathways or function as cyclic di-GMP or pGpG receptors. The few structures available indicate that HD-GYPs can be clustered into two distinct groups depending on the metal binding site, which can accommodate two or three metal ions. The nature and the number of bound metals determine whether a certain HD-GYP will be active as a PDE or will function as a dinucleotide binding domain. In this chapter, we will review the biochemical and structural data available to date on HD-GYPs.