Journal
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
Volume 67, Issue -, Pages 997-1008Publisher
WILEY-BLACKWELL
DOI: 10.1107/S090744491104039X
Keywords
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Funding
- Ministry of Education, Taiwan, ROC under the ATU
- National Science Council, Taiwan, ROC [97-2113-M005-005-MY3]
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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.
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