Sandbox Reserved 1063

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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Zinc-Dependent Transcriptional Regulator AdcRZinc-Dependent Transcriptional Regulator AdcR

IntroductionIntroduction

AdcR is a zinc-dependent transcriptional regulator that controls the activation of over seventy genes within the bacteria Streptococcus pneumoniae. Zinc plays a vital role in organism homeostasis acting as a [1] and a regulator of enzymatic activity, however zinc can lead to cell toxicity and deficiency of other vital metals that are also necessary for protein function. Given the fundamental role of zinc in general homeostasis the integral role of AdcR in Streptococcus pneumoniae can be seen.

Figure Legend

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Zinc-Dependent Transcriptional Regulator AdcR has on each of its two domains (important amino acids for zinc binding shown in white) and can bind a total of four zinc ions at one time. Of the two binding sites, binding site 1 is the only site with known importance for DNA binding. The function of binding site 2 is unknown.

Binding Site 1Binding Site 1

consists of a distorted tetrahedral geometry around the zinc ion. The four amino acids involved in zinc binding are E24, H42, H108, and H112.

Binding Site 2Binding Site 2

consists of a highly distorted tetrahedral geometry around the zinc ion. There are three amino acids involved in the binding of the zinc ion (C30, E41, and E107) as well as a water molecule. If a C30A mutation is present in binding site 1, it will have no effect on the ability of the protein to bind DNA. Therefore, binding site 2 has no significant role in DNA binding.

DNA BindingDNA Binding

Zinc's Allosteric ActivationZinc's Allosteric Activation

The binding of Zinc allows for the confirmational change that induces the binding of domain in order to activate genes. The binding of Zinc metals creates a hydrogen bond network within the protein that allows the DNA binding domain to wrap around DNA.

Helix-Turn-Helix DomainHelix-Turn-Helix Domain

The AdcR MarR transcriptional regulator's structure resembles the other proteins in the same family; however, the most notable differences are found in the winged helix-turn-helix (wHTH) motif that assists in binding DNA. This wHTH motif is consistent among all marR family proteins that bind DNA. Although AdcR is a highly alpha helical protein, the "wings" of the DNA binding domain consist of two anti parallel beta strands. There is one on each domain of the protein.

The HTH domain is made up of the alpha 2, alpha 3, alpha 4 helices. the alpha 4 helix is known as the recognition helix that binds the major groove of DNA through hydrogen bonding and Van der Waals interactions between exposed bases. The wings of the helix bind the minor groove of DNA while the other helices stabilize the DNA and Protein upon binding. The two anti parallel beta sheets contain several Arginine residues and other positive amino acids that stabilize this interaction between DNA.

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