4URG
Crystal Structure of GGDEF domain from T.maritima (active-like dimer)
Summary for 4URG
| Entry DOI | 10.2210/pdb4urg/pdb |
| Related | 4URQ 4URS |
| Descriptor | DIGUANYLATE CYCLASE, 9,9'-[(2R,3R,3aS,5S,7aR,9R,10R,10aS,12S,14aR)-3,5,10,12-tetrahydroxy-5,12-dioxidooctahydro-2H,7H-difuro[3,2-d:3',2'-j][1,3,7,9,2,8]tetraoxadiphosphacyclododecine-2,9-diyl]bis(2-amino-1,9-dihydro-6H-purin-6-one) (3 entities in total) |
| Functional Keywords | lyase |
| Biological source | THERMOTOGA MARITIMA |
| Total number of polymer chains | 2 |
| Total formula weight | 40541.85 |
| Authors | Deepthi, A.,Liew, C.W.,Liang, Z.X.,Swaminathan, K.,Lescar, J. (deposition date: 2014-06-30, release date: 2014-10-08, Last modification date: 2024-01-10) |
| Primary citation | Deepthi, A.,Liew, C.W.,Liang, Z.X.,Kunchithapadam, S.,Lescar, J. Structure of a Diguanylate Cyclase from Thermotoga Maritima: Insights Into Activation, Feedback Inhibition and Thermostability Plos One, 9:10912-, 2014 Cited by PubMed Abstract: Large-scale production of bis-3'-5'-cyclic-di-GMP (c-di-GMP) would facilitate biological studies of numerous bacterial signaling pathways and phenotypes controlled by this second messenger molecule, such as virulence and biofilm formation. C-di-GMP constitutes also a potentially interesting molecule as a vaccine adjuvant. Even though chemical synthesis of c-di-GMP can be done, the yields are incompatible with mass-production. tDGC, a stand-alone diguanylate cyclase (DGC or GGDEF domain) from Thermotoga maritima, enables the robust enzymatic production of large quantities of c-di-GMP. To understand the structural correlates of tDGC thermostability, its catalytic mechanism and feedback inhibition, we determined structures of an active-like dimeric conformation with both active (A) sites facing each other and of an inactive dimeric conformation, locked by c-di-GMP bound at the inhibitory (I) site. We also report the structure of a single mutant of tDGC, with the R158A mutation at the I-site, abolishing product inhibition and unproductive dimerization. A comparison with structurally characterized DGC homologues from mesophiles reveals the presence of a higher number of salt bridges in the hyperthermophile enzyme tDGC. Denaturation experiments of mutants disrupting in turn each of the salt bridges unique to tDGC identified three salt-bridges critical to confer thermostability. PubMed: 25360685DOI: 10.1371/JOURNAL.PONE.0110912 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
Download full validation report
