Sandbox Reserved 1063: Difference between revisions

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OCA, Zach LaRoche, Paxton Schowe, Geoffrey C. Hoops, Alexi Zaniker, Shandeep Singh, Isaac C. Gluesenkamp

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 Adhesin Competence Regulator (AdcR) is a transcriptional regulator that controls the activation of over seventy genes within the bacteria [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae''Streptococcus pneumoniae''] and is a member of the multiple antibiotic resistance regulator (MarR) protein family <ref>DOI:10.1093/nar/gku1304 </ref>. Members of the MarR protein family conserve a number of features including a general triangular shape, a two fold pseudosymmetric homo dimer, and a wingled helix-turn-helix pattern [https://en.wikipedia.org/wiki/Helix-turn-helix (wHTH)]. Consistent with AdcR's identity as a member of the MarR protein family, AdcR exhibits these conserved features. This structure calls for multiple zinc binding sites that facilitate protein conformational change allowing for DNA binding and regulation through the wHTH domain.
-Zinc plays a vital role in organism homeostasis acting as a [https://en.wikipedia.org/wiki/Cofactor_(biochemistry) co-factor] 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 <ref> Fraústo da Silva J, Williams R. The Biological Chemistry of Elements: The Inorganic Chemistry of Life. Second ed. Oxford University Press; Oxford: 2001.</ref><ref> DOI: 10.1021/cr900077w</ref>. The importance of AdcR in ''Streptococcus pneumoniae'' can be understood provided its ability to regulate zinc transfer proteins within the bacteria. Contrasting with other members of the MarR family, AdcR is metal dependent. Binding of Zinc allows AdcR to bind DNA and activate the transcription of high-affinity Zinc specific uptake transporters. The binding of Zinc induces a conformational change that allows for a hydrogen bond network between helices of the binding domain. It is believed that this hydrogen bond network is the allosteric activator needed to expose residues that bind the bases along the major groove of the DNA <ref>PMID:22085181</ref>.
+Zinc plays a vital role in organism homeostasis acting as a [https://en.wikipedia.org/wiki/Cofactor_(biochemistry) co-factor] 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 <ref> Fraústo da Silva J, Williams R. The Biological Chemistry of Elements: The Inorganic Chemistry of Life. Second ed. Oxford University Press; Oxford: 2001.</ref><ref> DOI: 10.1021/cr900077w</ref>. The importance of AdcR in ''Streptococcus pneumoniae'' can be understood provided its ability to regulate zinc transfer proteins within the bacteria. Contrasting with other members of the MarR family, AdcR is metal dependent. Binding of Zinc allows AdcR to bind DNA and activate the transcription of high-affinity Zinc specific uptake transporters. The binding of Zinc induces a conformational change that allows for a hydrogen bond network between helices of the binding domain. It is believed that this hydrogen bond network is the allosteric activator needed to expose residues that bind the bases along the major groove of the DNA <ref name="guerra">PMID:22085181</ref>.
 [[Image:Image1.jpg |300 px|left|thumb|Proteins 3BPX, 2FBK, 3KP5, and 2PFB (members of the MarR family) are pictured above.]]
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 == '''DNA Binding''' ==
 === Helix-Turn-Helix Motif ===
-The AdcR MarR transcriptional regulator's structure resembles the other proteins in the same family as mentioned before; however, the most notable differences are found in the winged helix-turn-helix (wHTH) motif that assists in binding DNA. This motif is characteristic of the MarR family and found within the DNA binding domain of the protein. The major groove of DNA is bound to the recognition helix while the wings of the motif grip onto the minor grooves of DNA <ref>PMID:22085181</ref>. Although AdcR is a highly alpha helical protein, the "wings" of the wHTH motif consist of two anti parallel beta strands that are made up of positively charged residues.
+The AdcR MarR transcriptional regulator's structure resembles the other proteins in the same family as mentioned before; however, the most notable differences are found in the winged helix-turn-helix (wHTH) motif that assists in binding DNA. This motif is characteristic of the MarR family and found within the DNA binding domain of the protein. The major groove of DNA is bound to the recognition helix while the wings of the motif grip onto the minor grooves of DNA <ref name="guerra" />. Although AdcR is a highly alpha helical protein, the "wings" of the wHTH motif consist of two anti parallel beta strands that are made up of positively charged residues.
 The <scene name='69/694230/Whth_2/1'>winged helix-turn-helix</scene> motif is made up of the <font color='blue'>alpha 2</font> and <font color='blue'>alpha 4 helices</font> along with <scene name='69/694230/Anti-parallel_beta_sheet/1'>anti-parallel beta sheets</scene> on each side. Only one monomer is shown for clarity purposes. There is one wHTH motif per monomer. The recognition helix, or the alpha 4 helix, 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 <scene name='69/694230/Positive_residues_on_wing/5'>Arginine, Asparagine, and Lysine residues</scene> that stabilize this interaction between DNA. The charge map down below highlights the dark blue tips consisting of lysine and arginine residues, which stabilize the negatively charged backbone of DNA.