A Unified Catalytic Mechanism for Cyclic di-NMP Hydrolysis by DHH–DHHA1 Phosphodiesterases

  • Lichuan GuEmail author
  • Qing He


Cyclic di-AMP is a vital second messenger other than cyclic di-GMP that regulates diverse cellular physiological processes in many bacteria. Its cellular level is controlled by the counter-actions of diadenylate cyclases (DAC) and phosphodiesterases (PDE). Three kinds of PDEs have been identified to date that contain either a DHH–DHHA1 domain, an HD domain, or a metallo-phosphoesterase domain, respectively. The DHH–DHHA1 PDEs are of special interest because of their functional diversity. They can be further subdivided into either membrane-bound GdpP or stand-alone Rv2837c phosphodiesterase, which degrade cyclic di-AMP into linear 5′-pApA and AMP, respectively. The DHH–DHHA1 PDEs can also hydrolyze other cyclic di-NMPs (cyclic di-GMP or cGAMP) with low activity. In this chapter, we review the structures and functions of the DHH–DHHA1 domain of GdpP and Rv2837c that we reported in recent years. According to detailed structural and enzymatic analyses, we have summarized a unified molecular mechanism for the DHH–DHHA1 PDEs and systematically analyzed the catalytic activities of DHH–DHHA1 PDEs on other cyclic di-NMPs (cyclic di-GMP and cGAMP).


Cyclic di-AMP Cyclic di-GMP PDEs DHH–DHHA1 GdpP Rv2837c 


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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.State Key Laboratory of Microbial TechnologyShandong UniversityQingdaoPeople’s Republic of China

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