3QYY

A Novel Interaction Mode between a Microbial GGDEF Domain and the Bis-(3, 5 )-cyclic di-GMP

Summary for 3QYY

• Entry DOI: 10.2210/pdb3qyy/pdb
• Descriptor: Response regulator, 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), DI(HYDROXYETHYL)ETHER, ... (5 entities in total)
• Functional Keywords: c-di-gmp, dgc, ggdef, competitive inhibition, xanthomonas campestris, signaling protein-inhibitor complex, signaling protein/inhibitor
• Biological source: Xanthomonas campestris pv. campestris
• Total number of polymer chains: 2
• Total formula weight: 39264.07

Authors

Yang, C.-Y.,Chin, K.-H.,Chou, S.-H. (deposition date: 2011-03-04, release date: 2011-11-30, Last modification date: 2024-03-20)

Primary citation

Yang, C.-Y.,Chin, K.-H.,Chuah, M.L.-C.,Liang, Z.-X.,Wang, A.H.-J.,Chou, S.-H.
The structure and inhibition of a GGDEF diguanylate cyclase complexed with (c-di-GMP)(2) at the active site
Acta Crystallogr.,Sect.D, 67:997-1008, 2011

PubMed Abstract: Cyclic diguanosine monophosphate (c-di-GMP) is a key signalling molecule involved in regulating many important biological functions in bacteria. The synthesis of c-di-GMP is catalyzed by the GGDEF-domain-containing diguanylate cyclase (DGC), the activity of which is regulated by the binding of product at the allosteric inhibitory (I) site. However, a significant number of GGDEF domains lack the RxxD motif characteristic of the allosteric I site. Here, the structure of XCC4471(GGDEF), the GGDEF domain of a DGC from Xanthomonas campestris, in complex with c-di-GMP has been solved. Unexpectedly, the structure of the complex revealed a GGDEF-domain dimer cross-linked by two molecules of c-di-GMP at the strongly conserved active sites. In the complex (c-di-GMP)(2) adopts a novel partially intercalated form, with the peripheral guanine bases bound to the guanine-binding pockets and the two central bases stacked upon each other. Alteration of the residues involved in specific binding to c-di-GMP led to dramatically reduced K(d) values between XCC4471(GGDEF) and c-di-GMP. In addition, these key residues are strongly conserved among the many thousands of GGDEF-domain sequences identified to date. These results indicate a new product-bound form for GGDEF-domain-containing proteins obtained via (c-di-GMP)(2) binding at the active site. This novel XCC4471(GGDEF)-c-di-GMP complex structure may serve as a general model for the design of lead compounds to block the DGC activity of GGDEF-domain-containing proteins in X. campestris or other microorganisms that contain multiple GGDEF-domain proteins.

PubMed: 22120736
DOI: 10.1107/S090744491104039X

Experimental method

X-RAY DIFFRACTION (1.9 Å)