Molecular basis for GTP recognition by light-activated guanylate cyclase RhGC
| Autor: | Allen M. Orville, Hadeeqa Raza, Heather Rada, A. Butryn, Raymond J. Owens, Isabel Moraes |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Models Molecular GTP' Stereochemistry Protein Conformation Guanosine Adenylate kinase Sequence Homology Crystallography X-Ray Biochemistry Cyclase retinylidene photoreceptor Catalysis Substrate Specificity Fungal Proteins 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine cyclic GMP Catalytic Domain Amino Acid Sequence Molecular Biology chemistry.chemical_classification Binding Sites guanylyl cyclase Substrate (chemistry) Cell Biology computer.file_format Original Articles Protein Data Bank Lyase 3. Good health cGMP guanylate cyclase 030104 developmental biology Enzyme chemistry 030220 oncology & carcinogenesis Original Article Guanosine Triphosphate computer Blastocladiomycota Protein Binding |
| Zdroj: | The Febs Journal |
| ISSN: | 1742-4658 1742-464X |
| Popis: | Cyclic guanosine 3′,5′‐monophosphate (cGMP) is an intracellular signalling molecule involved in many sensory and developmental processes. Synthesis of cGMP from GTP is catalysed by guanylate cyclase (GC) in a reaction analogous to cAMP formation by adenylate cyclase (AC). Although detailed structural information is available on the catalytic region of nucleotidyl cyclases (NCs) in various states, these atomic models do not provide a sufficient explanation for the substrate selectivity between GC and AC family members. Detailed structural information on the GC domain in its active conformation is largely missing, and no crystal structure of a GTP‐bound wild‐type GC domain has been published to date. Here, we describe the crystal structure of the catalytic domain of rhodopsin–GC (RhGC) from Catenaria anguillulae in complex with GTP at 1.7 Å resolution. Our study reveals the organization of a eukaryotic GC domain in its active conformation. We observe that the binding mode of the substrate GTP is similar to that of AC–ATP interaction, although surprisingly not all of the interactions predicted to be responsible for base recognition are present. The structure provides insights into potential mechanisms of substrate discrimination and activity regulation that may be common to all class III purine NCs. Database Structural data are available in Protein Data Bank database under the accession number 6SIR. Enzymes EC4.6.1.2. Synthesis of cGMP, an important intracellular signalling molecule, is catalysed by guanylate cyclases. Although detailed structural information is available, current data do not provide a sufficient explanation for the substrate selectivity between guanylate and adenylate cyclases. We present the crystal structure of the GTP‐bound catalytic domain of rhodopsin–GC from Catenaria anguillulae at 1.7 Å resolution. Our study provides insights into potential mechanisms of substrate discrimination and activity regulation. |
| Databáze: | OpenAIRE |
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