Sandbox Reserved 1072: Difference between revisions

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OCA, Elizabeth Hughes, Nicole Zimmerman, Geoffrey C. Hoops, David Emch, Isobel Bowles, Jack Trittipo

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 [[Image:C-di-GMP larger font.jpg |200 px|thumb|left|'''Figure 1: Cyclic-dimeric-GMP.''' Cyclic-dimeric-GMP is the product of the reaction catalyzed by DgcZ.]]
 [[Image:Poly B-1, 6 GlcNAc.jpg |150 px|left|thumb|'''Figure 2: Poly-β-1,6-N-acetylglucosamine.''' Poly-β-1,6-N-acetylglucosamine is a carbohydrate formed downstream of C-di-GMP utilized in formation of bacterial bio-films.]]
-Diguanylate cyclases are class 2 transferase enzymes <span class="plainlinks">[https://en.wikipedia.org/wiki/Diguanylate_cyclase (2.7.7.65)]</span> that catalyze the production of cyclic dimeric-guanosine monophosphate (c-di-GMP, Figure 1), important to <span class="plainlinks">[https://en.wikipedia.org/wiki/Signal_transduction signal transduction]</span> as a <span class="plainlinks">[https://en.wikipedia.org/wiki/Second_messenger_system second messenger]</span><sup>[1]</sup>. Signal transduction sends messages through cells to induce cellular responses, most commonly through phosphorylation or dephosphoylation of substrate molecules. <span class="plainlinks">[https://en.wikipedia.org/wiki/Escherichia_coli ''Escherechia coli (E. coli)'']</span>, a gram-negative bacterium often found in the intestines of mammals, uses diguanylate cyclase (DgcZ) in the synthesis of its <span class="plainlinks">[https://en.wikipedia.org/wiki/biofilm biofilm]</span><sup>[2]</sup>. DgcZ from ''E. coli'' acts as a catalyst, synthesizing C-di-GMP from two substrate guanosine triphosphate (GTP) molecules. C-di-GMP is a second messenger in the production of poly-β-1,6-N-acetylglucosamine (poly-GlcNAc, Figure 2), a polysaccharide required for ''E. coli'' biofilm production <sup>[2]</sup>. This biofilm allows ''E. coli'' to adhere to extracellular surfaces. Only the inactive conformation of the complete enzyme has been crystallized thus far <sup>[3]</sup>.
+Diguanylate cyclases are class 2 transferase enzymes <span class="plainlinks">[https://en.wikipedia.org/wiki/Diguanylate_cyclase (2.7.7.65)]</span> that catalyze the production of cyclic dimeric-guanosine monophosphate (c-di-GMP, Figure 1), important to <span class="plainlinks">[https://en.wikipedia.org/wiki/Signal_transduction signal transduction]</span> as a <span class="plainlinks">[https://en.wikipedia.org/wiki/Second_messenger_system second messenger]</span><sup>[1]</sup>. Signal transduction sends messages through cells to induce cellular responses, most commonly through phosphorylation or dephosphoylation of substrate molecules. <span class="plainlinks">[https://en.wikipedia.org/wiki/Escherichia_coli ''Escherechia coli (E. coli)'']</span>, a gram-negative bacterium often found in the intestines of mammals, uses diguanylate cyclase (DgcZ) in the synthesis of its <span class="plainlinks">[https://en.wikipedia.org/wiki/biofilm biofilm]</span><sup>[2]</sup>. DgcZ from ''E. coli'' acts as a catalyst, synthesizing C-di-GMP from two substrate guanosine triphosphate (GTP) molecules. C-di-GMP is a second messenger in the production of poly-β-1,6-N-acetylglucosamine (poly-GlcNAc, Figure 2), a polysaccharide required for ''E. coli'' biofilm production<sup>[2]</sup>. This biofilm allows ''E. coli'' to adhere to extracellular surfaces. Only the inactive conformation of the complete enzyme has been crystallized thus far<sup>[3]</sup>.
 [[Image:Conformation change 2 bold.png|250 px|right|thumb|'''Figure 3: Diagram of DgcZ.''' DgcZ is shown in its active (left) and inactive (right) conformations. The boxes represent the GGEEF domains of the enzyme, while the cylinders represent the alpha helices of the CZB domains, where the Zinc binding sites are located<sup>[3]</sup>. Binding Zn<sup>+2</sup> inactivates the enzyme. The red and blue sections represent the two monomers of the symmetric homodimer.]]
 == Structural Overview ==
 [[Image:DgcZ all domains sites labeled.png|250 px|left|thumb|'''Figure 4: Diguanylate cyclase DgcZ from ''E. Coli''.''' The two domains of the enzyme are labeled]]
-DgcZ is a dimeric protein with <scene name='69/694239/Dgcz_ggeef_dom_and_czb_dom/3'>two domains</scene> per monomer<sup>[4]</sup>. The DgcZ protein has <scene name='69/694239/C2_symmetry/6'>C2</scene> symmetry down its central axis. The catalytic glycine-glycine-glutamate-glutamate-phenylalanine (GGEEF) domains are responsible for synthesizing c-di-GMP. The regulatory chemoreceptor Zinc binding (CZB) domains house the two zinc binding sites. DgcZ binds Zinc in the CZB domains with sub-femtomolar (10<sup>-16</sup>M) affinity. When Zinc is bound, the CZB and GGEEF domains adopt conformations that inhibit DgcZ function, as illustrated in Figure 3<sup>[3]</sup>. Enzyme DgcZ was co-crystallized with Zinc, fixing the structure in its inactivate conformation. The GGEEF domains are catalytic, containing the active sites used for cyclizing GTP into c-di-GMP. The CZB domains are used for ligand-mediated regulation of c-di-GMP production and have an important role in signal transduction of bacteria. CZB and GGEEF domains are found in proteins from many bacterial lineages, including DgcZ homologs<sup>[5]</sup>.
+DgcZ is a dimeric protein with <scene name='69/694239/Dgcz_ggeef_dom_and_czb_dom/3'>two domains</scene> per monomer<sup>[4]</sup>. The DgcZ protein has <scene name='69/694239/C2_symmetry/6'>C2</scene> symmetry down its central axis. The catalytic glycine-glycine-glutamate-glutamate-phenylalanine (GGEEF) domains are responsible for synthesizing c-di-GMP. The regulatory chemoreceptor Zinc binding (CZB) domains house the two zinc binding sites, one site located on each monomer. DgcZ binds Zinc in the CZB domains with sub-femtomolar (10<sup>-16</sup>M) affinity. When Zinc is bound, the CZB and GGEEF domains adopt conformations that inhibit DgcZ function, as illustrated in Figure 3<sup>[3]</sup>. Enzyme DgcZ was co-crystallized with Zinc, fixing the structure in its inactivate conformation. The GGEEF domains are catalytic, containing the active sites for cyclizing GTP into c-di-GMP. The CZB domains are used for ligand-mediated regulation of c-di-GMP production and have an important role in signal transduction of bacteria. CZB and GGEEF domains are found in proteins from many bacterial lineages, including DgcZ homologs<sup>[5]</sup>.
 ==Catalytic GGEEF Domains==