Assignments got your hair on fire?

Douse the flames with our full-range writing service!

Experienced academic writing professionals are at your fingertips. Use this handy tool to get a price estimate for your project.

Cyclic guanosine monophosphate - Wikipedia

Richter, AM, Povolotsky, TL, Wieler, LH, Hengge, R. Cyclic‐di‐GMP signalling and biofilm‐related properties of the Shiga toxin‐producing 2011 German outbreak O104:H4. EMBO Mol Med 2014, 6:1622–1637.

Hu, J, Wang, B, Fang, X, Means, WJ, McCormick, RJ, Gomelsky, M, Zhu, MJ. c‐di‐GMP signaling regulates O157:H7 adhesion to colonic epithelium. Vet Microbiol 2013, 164:344–351.

Hengge, R. Principles of c‐di‐GMP signalling in bacteria. Nat Rev Microbiol 2009, 7:263–273.

Cyclic guanosine monophosphate (cGMP) ..

Chambers, JR, Liao, J, Schurr, MJ, Sauer, K. BrlR from  is a c‐di‐GMP‐responsive transcription factor. Mol Microbiol 2014, 92:471–487.

Weber, H, Pesavento, C, Possling, A, Tischendorf, G, Hengge, R. Cyclic‐di‐GMP‐mediated signalling within the sigma network of . Mol Microbiol 2006, 62:1014–1034.

Raterman, EL, Shapiro, DD, Stevens, DJ, Schwartz, KJ, Welch, RA. Genetic analysis of the role of in the ability of CFT073 to control cellular cyclic dimeric GMP levels and to persist in the urinary tract. Infect Immun 2013, 81:3089–3098.

Guanylate cyclase (GC) catalyzes cGMP synthesis.

Conner, JG, Zamorano‐Sanchez, D, Park, JH, Sondermann, H, Yildiz, FH. The ins and outs of cyclic di‐GMP signaling in . Curr Opin Microbiol 2017, 36:20–29.

Filloux, biofilms and cyclic di-GMP (c-di-GMP) signaling: lessons from Pseudomonas aeruginosa and other bacteria

Comparing the structures of the c-di-GMP-activated and resting states of the BcsA–B complex, at intermediate states during cellulose translocation provides unique insights into the mechanism of cellulose biosynthesis. In the absence of c-di-GMP, BcsA is catalytically inactive and its gating loop blocks the entrance to the active site,. Allosteric activation by c-di-GMP displaces the gating loop from the active site, thereby forming a large opening towards the substrate-binding pocket, wide enough for substrate diffusion. However, opening and closing the active site is unlikely to be the only function of BcsA’s gating loop. When UDP binds to the active site, the gating loop inserts deeply into the catalytic pocket and coordinates the nucleotide via conserved residues. Most likely, this also reflects how BcsA interacts with its substrate UDP-Glc, positioning it for catalysis, excluding water from the active site and perhaps also stabilizing the UDP leaving group during glycosyl transfer. A similar mechanism of substrate-dependent loop insertion and de-insertion has been described for non-processive galactosyltransferases,. The functional importance of the gating loop is further underlined by its sequence homology with the location of the isoxaben resistance mutation in Arabidopsis thaliana cellulose synthase 3 (). Here, Thr942 of the “FxVTxK” motif is mutated to Ile, thereby allowing growth in the presence of the herbicide isoxaben. However, because pro- and eukaryotic cellulose synthases differ in their predicted TM topologies, further experimental analyses are required to confirm a similar eukaryotic gating loop function.

Versatile Services that Make Studying Easy
We write effective, thought-provoking essays from scratch
We create erudite academic research papers
We champion seasoned experts for dissertations
We make it our business to construct successful business papers
What if the quality isn’t so great?
Our writers are sourced from experts, and complete an obstacle course of testing to join our brigade. Ours is a top service in the English-speaking world.
How do I know the professor won’t find out?
Everything is confidential. So you know your student paper is wholly yours, we use CopyScape and WriteCheck to guarantee originality (never TurnItIn, which professors patrol).
What if it doesn’t meet my expectations?
Unchanged instructions afford you 10 days to request edits after our agreed due date. With 94% satisfaction, we work until your hair is comfortably cool.
Clients enjoy the breezy experience of working with us
Click to learn our proven method

Download Cyclic GMP: Synthesis, Metabolism, and …


Cyclic GMP synthesis and function (PDF Download …

In order to unravel the mechanism by which c-di-GMP activates bacterial cellulose synthase, we determined c-di-GMP-bound structures of the Rhodobacter sphaeroides BcsA–B complex at intermediate states during cellulose synthesis and translocation. The c-di-GMP-bound structures reveal the architecture of the activated BcsA–B complex and provide unique insights into the mechanism of c-di-GMP signaling. These include the identification of a conserved regulatory salt bridge that auto-inhibits BcsA in the absence of c-di-GMP and the UDP-dependent repositioning of a gating loop to either open the catalytic pocket or to coordinate the nucleotide at the active site. Furthermore, the structures reveal the movement of a “finger helix” of BcsA, which interacts with the acceptor end of the translocating cellulose polymer, towards the TM channel entrance, correlating with the translocation of the cellulose polymer into the channel by one glucose unit. Thus, our data provide the first insights into the mechanism by which c-di-GMP modulates enzymatic functions and represent novel snapshots of cellulose synthesis and membrane translocation.

Cyclic GMP : synthesis, metabolism, and function …

Extracellular polysaccharides of the biofilm matrix, such as cellulose, alginate and poly-N-acetylglucosamine (PNAG), are likely synthesized and secreted by a conserved mechanism. Bacterial cellulose synthase polymerizes glucose molecules via β-1,4 glycosidic linkages in a multi-step process which requires the presence of a divalent cation, mostly magnesium. First, upon stimulation by c-di-GMP, the enzyme binds its substrate UDP-Glc (donor) at an intracellular glycosyltransferase (GT) domain. Second, the donor glucose is transferred to the 4′ hydroxyl group at the non-reducing end of the growing polysaccharide chain (acceptor), thereby extending the polymer and forming UDP as a second reaction product,. Third, following glycosyl transfer, the elongated polymer has to be translocated by one glucose unit into a transmembrane (TM) channel so that the newly added glucose unit occupies the acceptor site and UDP must be replaced with UDP-Glc for another round of catalysis.

Cyclic GMP : synthesis, metabolism, and function

Indeed, disrupting this salt bridge by replacing Glu371 with Ala increases the enzyme’s catalytic activity in the absence of c-di-GMP approximately 6-fold compared to the wild type enzyme, (). Under these conditions, Arg580 may still be able to interact with the gating loop’s backbone. However, replacing Arg580 with Ala, either in the wild type or E371A background, renders BcsA constitutively active as observed by quantifying the formation of each reaction product, cellulose ( and ) or UDP (). Importantly, the R580A mutant still binds c-di-GMP, although with slightly reduced affinity (); yet, even at a c-di-GMP concentration more than 50-fold above its dissociation constant, no further stimulation of cellulose biosynthesis is observed (). These observations suggest that the Arg580-Glu371 salt bridge and the subsequent interaction of Arg580 with the gating loop are responsible for auto-inhibiting the synthase. This inhibition is then released when Arg580 rotates away from the GT domain to interact with c-di-GMP.

[Ferid Murad;] -- This volume is dedicated to the topic of cyclic GMP

Biofilms are sessile multi-cellular bacterial communities that are encased in a 3-dimensional meshwork of biopolymers, such as polysaccharides, proteinaceous filaments and nucleic acids. The biofilm matrix provides protection against mechanical stress, and controls the diffusion of signaling molecules, nutrients and toxic compounds. In fact, biofilm communities exhibit increased tolerance towards conventional anti-microbial treatments and sterilization techniques and are responsible for many chronic infections associated with cystic fibrosis and endocarditis, as well as nosocomial infections. In many cases, biofilm formation occurs in response to an elevated cytosolic concentration of cyclic-di-GMP (c-di-GMP), a bacterial signaling molecule recognized by a wide range of effector proteins, including transcription factors, flagellar components, riboswitches and exopolysaccharide synthases. Therefore, targeting c-di-GMP–binding effectors has emerged as an attractive new route for the development of urgently needed novel anti-microbial therapeutics.

Cyclic di-GMP (also called cyclic ..

The bacterial signaling molecule cyclic-di-GMP stimulates the synthesis of bacterial cellulose, frequently found in biofilms. Bacterial cellulose is synthesized and translocated across the inner membrane by a complex of the cellulose synthase BcsA and BcsB subunits. Here we present crystal structures of the cyclic-di-GMP-activated BcsA–B complex. The structures reveal that cyclic-di-GMP releases an auto-inhibited state of the enzyme by breaking a salt bridge which otherwise tethers a conserved gating loop that controls access to and substrate coordination at the active site. Disrupting the salt bridge by mutagenesis generates a constitutively active cellulose synthase. Additionally, the cyclic-di-GMP activated BcsA–B complex contains a nascent cellulose polymer whose terminal glucose unit rests at a novel location above BcsA’s active site where it is positioned for catalysis. Our mechanistic insights are the first examples of how cyclic-di-GMP allosterically modulates enzymatic functions.

89%
of clients claim significantly improved grades thanks to our work.
98%
of students agree they have more time for other things thanks to us.
Clients Speak
“I didn’t expect I’d be thanking you for actually improving my own writing, but I am. You’re like a second professor!”