title: Cyclic Nucleotide Monophosphates in Plants and Plant Signaling.
abstract: Cyclic nucleotide monophosphates (cNMPs) and the enzymes that can generate them are of increasing interest in the plant sciences. Arguably, the major recent advance came with the release of the complete Arabidopsis thaliana genome that has enabled the systematic search for adenylate (ACs) or guanylate cyclases (GCs) and did eventually lead to the discovery of a number of GCs in higher plants. Many of these proteins have complex domain architectures with AC or GC centers moonlighting within cytosolic kinase domains. Recent reports indicated the presence of not just the canonical cNMPs (i.e., cAMP and cGMP), but also the noncanonical cCMP, cUMP, cIMP, and cdTMP in plant tissues, and this raises several questions. Firstly, what are the functions of these cNMPs, and, secondly, which enzymes can convert the substrate triphosphates into the respective noncanonical cNMPs? The first question is addressed here by comparing the reactive oxygen species (ROS) response of cAMP and cGMP to that elicited by the noncanonical cCMP or cIMP. The results show that particularly cIMP can induce significant ROS production. To answer, at least in part, the second question, we have evaluated homology models of experimentally confirmed plant GCs probing the substrate specificity by molecular docking simulations to determine if they can conceivably catalytically convert substrates other than ATP or GTP. In summary, molecular modeling and substrate docking simulations can contribute to the evaluation of cyclases for noncanonical cyclic mononucleotides and thereby further our understanding of the molecular mechanism that underlie cNMP-dependent signaling in planta.
authors.affiliation: Department of Biochemistry, Cambridge Centre for Proteomics, University of Cambridge, Cambridge, UK.
authors.forename: Claudius
authors.initials: C
authors.lastname: Marondedze
authors.affiliation: Division of Biological and Environmental Science and Engineering, King Abdullah University of Science and Technology, Thuwal, Kingdom of Saudi Arabia.
authors.forename: Aloysius
authors.initials: A
authors.lastname: Wong
authors.affiliation: Proteomics Core Laboratory, King Abdullah University of Science and Technology, Thuwal, Kingdom of Saudi Arabia.
authors.forename: Ludivine
authors.initials: L
authors.lastname: Thomas
authors.affiliation: Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia.
authors.forename: Helen
authors.initials: H
authors.lastname: Irving
authors.affiliation: Division of Biological and Environmental Science and Engineering, King Abdullah University of Science and Technology, Thuwal, Kingdom of Saudi Arabia. christoph.gehring@kaust.edu.sa.
authors.forename: Chris
authors.initials: C
authors.lastname: Gehring
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000737:chemistry / Q000378:metabolism; D002384:Catalysis; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D008958:Models, Molecular; D009712:Nucleotides, Cyclic / Q000378:metabolism*; D010940:Plant Proteins / Q000737:chemistry / Q000378:metabolism; D010944:Plants / Q000378:metabolism*; D011487:Protein Conformation; D017382:Reactive Oxygen Species / Q000378:metabolism; D015290:Second Messenger Systems; D000071756:Soluble Guanylyl Cyclase / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D009712:Nucleotides, Cyclic; D010940:Plant Proteins; D017382:Reactive Oxygen Species; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP
keywords: Adenylate cyclase; Arabidopsis thaliana; Cyclic nucleotide monophosphates; Guanylate cyclase; Plant; Second messenger; cAMP; cGMP