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This Sandbox is Reserved from 02/09/2015, through 05/31/2016 for use in the course "CH462: Biochemistry 2" taught by Geoffrey C. Hoops at the Butler University. This reservation includes Sandbox Reserved 1051 through Sandbox Reserved 1080.

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Contents 1 DgcZ from E. coli 2 Structure 2.1 Catalytic GGDEF Domain 2.2 CZB Domain 3 Mechanism of Action 4 Zinc Ligand(s) 4.1 Inhibition 5 Other Ligands 6 References

DgcZ from E. coli

Diguanylate cyclases synthesize cyclic dimeric-GMP (c-di-GMP) from two GTP molecules. C-di-GMP is a second messenger in the production of poly-β-1,6-N-acetylglucosamine (poly-GlcNAc) , a polysaccharide required for E. coli biofilm production. This biofilm allows E. coli to adhere to extracellular surfaces. The DgcZ protein is made of two domains: the catalytic GGDEF domain responsible for sythnesizing c-di-GMP and the regulatory CZB domain that binds zinc. When zinc is bound, the CZB and GGDEF domains adopt conformations that inhibit DgcZ function. DgcZ binds zinc with sub-femtomolar affinity, making it very likely that zinc will bind in the CZB domain.

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Structure

Catalytic GGDEF Domain

E. coli DgcZ is a protein made of two domains each of which is a symmetric homodimer. The GGDEF domain is made of a central five-stranded β-sheet with five α-helices surrounding it. Each dimer contains an active half-site that, when combined together in a productive conformation, form the entire active site. Each half-site binds one GTP. The guanyl base forms hydrogen bonds with asparagine-173 and aspartate-182 to hold it in the active site. A magnesium²⁺ ion stabilizes the negative charges on the phosphate groups. When in the productive conformation, each GTP is held in close proximity with the α-phosphate groups overlapping C3 of the ribose. This conformation allows the α-phospate of one GTP to react with alcohol on C3 on the ribose of the other GTP, resulting in a cyclization of the two molecules into cyclic-dimeric-GMP.

CZB Domain

Mechanism of Action

Zinc Ligand(s)

Inhibition

Other Ligands

References