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Thread: Designer enzymes

  1. #131
    tWebber shunyadragon's Avatar
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    Quote Originally Posted by lee_merrill View Post
    Here they describe precursors to nucleotides and lipids and amino acids. In my example, I assume the presence of nucleotides in abundance. You still need a ribozyme to assemble, for instance.

    Blessings,
    Lee
    You need to read the references and respond coherently, which you have failed to do. You are trying to herd jelly fish.
    Glendower: I can call spirits from the vasty deep.
    Hotspur: Why, so can I, or so can any man;
    But will they come when you do call for them? Shakespeare’s Henry IV, Part 1, Act III:

    go with the flow the river knows . . .

    Frank

    I do not know, therefore everything is in pencil.

  2. #132
    tWebber shunyadragon's Avatar
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    Quote Originally Posted by lee_merrill View Post
    Yes, they do form randomly, if they do not replicate.
    Ribosomes form by the Laws of Nature reflected in the laws of chemistry.

    But repeating the question will not change my reply: I selected a biomolecule that is not self-replicating, so it has to form randomly. You need replication and competition for natural selection, for evolution to work.
    The original ribosomes from by organic chemistry and not replication. It is understood that ribosomes do not replicate themselves.

    You have not responded to the references. It is more than obvious that you do not understand them.

    Well, what distribution would explain the interactions of molecules in solution, if not a uniform random one?
    No the laws of nature reflected in chemistry determine the interactions of the molecules.
    Glendower: I can call spirits from the vasty deep.
    Hotspur: Why, so can I, or so can any man;
    But will they come when you do call for them? Shakespeare’s Henry IV, Part 1, Act III:

    go with the flow the river knows . . .

    Frank

    I do not know, therefore everything is in pencil.

  3. #133
    tWebber HMS_Beagle's Avatar
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    Quote Originally Posted by shunyadragon View Post
    Your moving around the goal posts and basing your argument on the very jello-like 'argument of ignorance' concerning the the question of the origin of the ribosomes, and actually not reading the references, and NOT responding to the references, nor The Lurch,.

    Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2926754/



    Origin and Evolution of the Ribosome
    George E. Fox

    Abstract
    The modern ribosome was largely formed at the time of the last common ancestor, LUCA. Hence its earliest origins likely lie in the RNA world. Central to its development were RNAs that spawned the modern tRNAs and a symmetrical region deep within the large ribosomal RNA, (rRNA), where the peptidyl transferase reaction occurs. To understand pre-LUCA developments, it is argued that events that are coupled in time are especially useful if one can infer a likely order in which they occurred. Using such timing events, the relative age of various proteins and individual regions within the large rRNA are inferred. An examination of the properties of modern ribosomes strongly suggests that the initial peptides made by the primitive ribosomes were likely enriched for l-amino acids, but did not completely exclude d-amino acids. This has implications for the nature of peptides made by the first ribosomes. From the perspective of ribosome origins, the immediate question regarding coding is when did it arise rather than how did the assignments evolve. The modern ribosome is very dynamic with tRNAs moving in and out and the mRNA moving relative to the ribosome. These movements may have become possible as a result of the addition of a template to hold the tRNAs. That template would subsequently become the mRNA, thereby allowing the evolution of the code and making an RNA genome useful. Finally, a highly speculative timeline of major events in ribosome history is presented and possible future directions discussed.

    A major commonality of all cellular life is the coupling between translation and transcription mediated by the genetic code. Comparative genomics has further refined this by revealing the presence of an “RNA metabolism” (Anantharaman et al. 2002) or “Persistent proteome” (Danchin et al. 2007) that is basically a compendium of essentially universal genes involved in translation, transcription, RNA processing and degradation, intermediary and RNA metabolism, and compartmentalization. DNA replication likely arose later because the core enzymes involved in the process are not related (Bailey et al. 2006 and others). Together these universal genes comprise what is frequently referred to as LUCA, the last universal common ancestor (Benner et al. 1993; Lazcano 1994; Mushegian and Koonin 1996; Kyrpides et al. 1999). It is noteworthy that no matter how they are defined, by far the largest numbers of genes in LUCA are associated with translation. Indeed, the translation machinery as represented in LUCA is essentially complete indicating that major events in its origins occurred before LUCA. Thus, it might appear that the origins of the translation machinery would be hopelessly obscured by time. Nevertheless, as will be discussed herein, substantial although necessarily incomplete, evidence relating to the origins and early development of the translation machinery and its relation to other core cellular processes continues to exist in the primary sequences, three-dimensional folding, and functional interactions of the various macromolecules involved in the modern versions of the translation machinery.

    The modern ribosome consists of small and large subunits (30S and 50S in Bacteria and Archaea) that come together during the initiation of protein synthesis remain together as individual amino acids are added to a growing peptide according to information encoded on the mRNA, and finally separate again in conjunction with the release of the finished protein. Each subunit is an RNA/protein complex. In Bacteria and Archaea, the 50S subunit typically contains a 23S rRNA and a 5S rRNA whereas the 30S subunit contains the 16S rRNA. Peptide bond synthesis occurs in the 50S subunit at the peptidyl transferase center, (PTC), and codon recognition occurs at the decoding site, which is in the small subunit. Transfer RNAs, (tRNA), bridge the two subunits occupying, at various times in the synthesis cycle, the A, P, or E (exit) sites of the 50S subunit and the decoding site in the 30S subunit. A universal CCA sequence at the 3′ end of the tRNA is the point of attachment of the amino acid and later the growing peptide chain to the tRNA. The A, P, and E sites are partly in the small subunit and partly in the large subunit such that a tRNA can be in a hybrid site (e.g., the A site in the 30S and P site in the 50S. The mRNA is exclusively found in the small subunit where it interacts with the anticodon loops of the tRNAs. As the nascent protein is synthesized it passes through an exit tunnel that begins at the PTC center and ultimately exits from the back of the 50S subunit. Synthesis is a dynamic cyclic process in which tRNAs enter the ribosome bringing amino acids as specified by the mRNA and move through the machinery, which undergoes a series of coordinated motions that drive the process (Steitz 2008). These include the movements of the tRNAs between sites, opening and closing of the L1 stalk on the 50S subunit and the ratcheting of the small subunit relative to the large subunit (Frank and Agrawal, 2000), which has recently been elucidated in structural detail (Zhang et al. 2009).

    Diverse species (Escherichia coli, Haloarcula marismortui, Thermus thermophiles, and Deinococcus radiodurans) are represented among the various atomic resolution ribosome structures now available (Ban et al. 2000; Yusupov et al. 2000; Wimberly et al. 2000; Schuwirth et al. 2005; Selmer et al. 2006; and others). These structures encompass 30S and 50S subunits as well as the whole 70S ribosome. In addition, cryoelectron microscopy studies have revealed dynamic motions associated with the ribosome (Frank and Agrawal 2000; Connell et al. 2007; and others). These ongoing high resolution structural studies provide the opportunity to examine the relative age of features within the ribosome such as the A, P, and E sites, the exit tunnel, the L7/L12 region, and the L1 region that facilitate the entry and exit of tRNAs.


    It is believed that the peptidyl transferase center, (PTC), which encompasses the large subunit portions of the A and P sites of the ribosome, is structurally the same in both the 50S and 70S subunits (Steitz 2008). When comparing 50S subunit structures between Archaea and Bacteria one again finds that the structures are essentially the same. However, the E site structure is different. In Archaea L44e interacts with the E-site tRNA but this protein is missing in Bacteria with the result that the tRNA CCA end is positioned differently. Hence, the A and P sites likely predate the E site, which may have been added post-LUCA (Steitz 2008).

    The portion of 23S rRNA comprising the PTC contains a region of approximately 165 bases that shows high twofold pseudo symmetry (Agmon et al. 2005; Zimmerman & Yonath 2009). The two 82 nucleotide halves of the symmetrical region correspond to the 50S portion of the A and P sites of the ribosome. In fact, the essence of this region is contained in a single contiguous self-folding RNA (Smith et al. 2008). The PTC is located in Domain 5 of the 23S rRNA structure.

    Recently, Hsiao et al. (2009) superimposed the structure of the large subunit RNAs from two ribosome crystal structures and sectioned the resulting structure into concentric shells with the PTC at the center. They, like others (Ban et al. 2000; Wimberly et al. 2000), found that ribosomal proteins (r-proteins) are effectively absent from the PTC region, which is why the ribosome is regarded as fundamentally an RNA machine. To the extent that protein elements are in proximity to the PTC, they are short, largely unstructured peptides rather than globular elements. The globular regions are mainly on the surface of the ribosome (Ban et al. 2000; Wimberly et al. 2000). A major stabilizing element in the PTC region is instead Mg2+ interactions. In many cases, the phosphate oxygen atoms act as inner sphere Mg2+ ligands (Hsiao et al. 2009; Hsiao and Williams 2009). Thus, consistent with the notion of a preceding RNA world, the structure of the PTC seems to have evolved before the availability of proteins.

    Although the modern translation machinery is very complex, two small RNAs, the PTC RNA fragment and tRNAs are at its core. Both of these are less than 100 nucleotides in length, and their importance supports the notion that the translation machinery was originally a discovery of the RNA world. In fact, the ability to synthesize coded peptides of increasing complexity would eventually terminate the RNA world and create the RNA/protein world. The seldom discussed issue is whether such a termination would have occurred before (e.g., brief RNA world) or after the discovery of an RNA replicase (extended RNA world). If peptide synthesis arises quickly, then their will neither be time nor need for extensive catalysis of biochemical reactions by RNA. If reasonable, the rapid appearance of a translation system may even eliminate the need to validate the RNA world by demonstrating the self-replicating RNA system that has proven experimentally difficult to achieve.

    Go to:
    tRNA ORIGINS AND INCREASING RNA COMPLEXITY
    Because of its obvious importance, considerable attention has been focused on the origins of the tRNA and numerous models have been proposed and recently reviewed (Di Giulio 2009). The most popular model (Noller 1993; Maizels and Weiner 1993 and 1994; Schimmel et al. 1993; Schimmel and Henderson 1994), envisions the tRNA as having two domains, each encompassing half the molecule. One domain contains the terminal CCA sequence to which the incoming amino acid or growing peptide is attached. The second domain contains the anticodon and associated loop that interact with the mRNA. The two domains are frequently envisioned as being of different age with the CCA domain being older. Support for this idea stems from the fact that the CCA domain alone forms a “minihelix” to which modern tRNA synthetases can readily attach specific amino acids. Such aminoacylation has also been shown with evolved ribozymes (Lee et al. 2000), which can be surprisingly small (Chumachenko et al. 2009). In fact, aminoacylation has been reported without any enzyme or ribozyme at all (Tamura and Schimmel 2004). Furthermore, it has also been reported that a minihelix when incorporated into the 50S subunit can participate in peptide bond formation (Sardesai et al. 1999). Indeed, even the addition of a single cytosine (equivalent to C75 of modern tRNAs) to puromycin is apparently sufficient to allow peptide bond formation (Brunelle et al. 2006). Thus, it may initially only be necessary to have the CCA segment alone (Nissen et al. 2000). The 5′ domain of the tRNA is not consequential to peptide bond formation and could have been added later. If the tRNAs evolved from the one domain structure or an even simpler structure, then protein synthesis would likely have begun as a noncoded process (Schimmel and Henderson 1994). Single domain or even smaller aminoacylated RNAs are especially attractive in an RNA world where synthesis of larger RNAs is likely to be difficult. Synthesis of random oligomers in the 20–40 size range has been shown (Joshi et al. 2009; Powner et al. 2009; Szostak, 2009; Ferris et al. 1996) but the path to prebiotic synthesis of large RNAs is not without difficulties (Orgel, 2004).

    How does one obtain RNAs of increasing complexity, such as those of modern tRNAs or the PTC RNA, without a true RNA replicase? There are two core possibilities, ligation and hybridization. RNA ligation has been shown to be feasible in an RNA World (Hager et al. 1996; Hager and Szostak 1997; McGinness and Joyce 2002). Thus, it is of interest that the tRNA “cloverleaf” secondary structure can be formed by a direct duplication, e.g., ligation, of an appropriate stem loop structure (Di Guilio 2002). The possible relevance of this idea was enhanced further by the demonstration that it was possible to actually replicate all the major tertiary interactions seen in modern tRNAs when two appropriate stem loop structures were ligated together (Nagaswamy and Fox 2003).

    An alternative method of readily obtaining more complex structures is to simply hybridize small fragments to one another such that a larger RNA with many “nicks” is assembled. These nicks might or might not be sealed at a later stage. In Nanoarchaeum equitans, several tRNAs are encoded as partially complementary half molecules, which are then ligated together to form a tRNA (Randau et al. 2005a and b). In Euglena gracillis the large subunit rRNA is comprised of 14 discrete RNA fragments held together by hybridization events that form various helical elements. Not only are the fragments not coded in the order they appear in the final RNA but they are actually intermingled in the genome with similar fragments of the small subunit RNA (Smallman et al. 1996).

    © Copyright Original Source



    It may help if you read the whole article, and respond to the other posts and references you have avoided.
    Lee still has his "Pants On Fire" hat on. He isn't interested in learning the science, just preaching. Same as it always is with Dory.

  4. #134
    tWebber lee_merrill's Avatar
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    Quote Originally Posted by shunyadragon View Post
    Ribosomes form by the Laws of Nature reflected in the laws of chemistry.
    But I was talking about a ribozyme, not a ribosome. The ribosome is much more complex.

    You have not responded to the references. It is more than obvious that you do not understand them.
    Which references have I not responded to, though?

    No the laws of nature reflected in chemistry determine the interactions of the molecules.
    Which laws of nature? I believe that molecular interactions in a chemical reaction are characterized by a uniform probability distribution.

    Blessings,
    Lee
    "What I pray of you is, to keep your eye upon Him, for that is everything. Do you say, 'How am I to keep my eye on Him?' I reply, keep your eye off everything else, and you will soon see Him. All depends on the eye of faith being kept on Him. How simple it is!" (J.B. Stoney)

  5. #135
    tWebber lee_merrill's Avatar
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    Quote Originally Posted by shunyadragon View Post
    Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2926754/



    Origin and Evolution of the Ribosome

    © Copyright Original Source


    Again, I was estimating the creation of a ribozyme, not a ribosome.

    Blessings,
    Lee
    "What I pray of you is, to keep your eye upon Him, for that is everything. Do you say, 'How am I to keep my eye on Him?' I reply, keep your eye off everything else, and you will soon see Him. All depends on the eye of faith being kept on Him. How simple it is!" (J.B. Stoney)

  6. #136
    tWebber HMS_Beagle's Avatar
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    Quote Originally Posted by lee_merrill View Post
    Again, I was estimating the creation of a ribozyme, not a ribosome.
    By pulling a number straight out of where the sun doesn't shine. Another Dory moment.

    Evolution of Ribozymes in an RNA World
    Muller
    Chemistry & Biology Vol 16, Issue 8, 28 Aug. 2009, pp 797-798

    Overview: Ribozymes (catalytic RNAs) were the center of a presumed RNA world in the early origin of life. In this issue, Lau and Unrau show evidence that an RNA world could have used a similar evolutionary pathway as most proteins do.
    The paper

    A Promiscuous Ribozyme Promotes Nucleotide Synthesis in Addition to Ribose Chemistry
    Lau, Unrau
    Chemistry & Biology Vol 16, Issue 8, 28 Aug 2009, pp 815-825

    Summary: Here we report the in vitro selection of an unusual ribozyme that efficiently performs nucleotide synthesis even though it was selected to perform a distinctly different sugar chemistry. This ribozyme, called pR1, when derivatized with ribose 5-phosphate (PR) at its 3′ terminus and incubated with 6-thioguanine, produces two interconverting thiol-containing products corresponding to a Schiff base and its Amadori rearranged product. Consistent with this hypothesis, removing the 2-hydroxyl from the PR substrate results in only a single product. Surprisingly, as this was not selected for, switching the tethered PR substrate to 5-phosphoribosyl 1-pyrophosphate results in the synthesis of 6-thioguanosine 5′-monophosphate. The discovery that a ribozyme can promote such distinct reactions spontaneously demonstrates that an RNA-mediated metabolism early in evolution could have evolved important new functionalities via ribozyme promiscuity
    Lee will now either lie about this data or ignore it.

  7. #137
    tWebber lee_merrill's Avatar
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    Source: Muller

    The first pathway would have been most important in the beginning of the RNA world, where ribozymes would have to appear de novo from more or less random sequences.

    © Copyright Original Source


    Right, the first ribozyme would have to appear de novo, randomly. Then they state "by amplification of the fittest", which I expect explains "more or less random sequences", and this is offered without any explanation that I can see. But for any amplification of the fittest to occur, there need to be repeated ribozymes, and the probability of that appears to be astronomical.

    And I'm not sure why you posted the second paper, it doesn't seem to address ribozyme genesis at all.

    Blessings,
    Lee
    "What I pray of you is, to keep your eye upon Him, for that is everything. Do you say, 'How am I to keep my eye on Him?' I reply, keep your eye off everything else, and you will soon see Him. All depends on the eye of faith being kept on Him. How simple it is!" (J.B. Stoney)

  8. #138
    tWebber HMS_Beagle's Avatar
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    Quote Originally Posted by lee_merrill View Post
    Source: Muller

    The first pathway would have been most important in the beginning of the RNA world, where ribozymes would have to appear de novo from more or less random sequences.

    © Copyright Original Source


    Right, the first ribozyme would have to appear de novo, randomly. Then they state "by amplification of the fittest", which I expect explains "more or less random sequences", and this is offered without any explanation that I can see. But for any amplification of the fittest to occur, there need to be repeated ribozymes, and the probability of that appears to be astronomical.

    And I'm not sure why you posted the second paper, it doesn't seem to address ribozyme genesis at all.
    Exactly as expected Lee quote-mines and lies about the paper. BTW Dory the first link is the summary of the paper, the second is the paper itself.

    Dory is nothing if not predictable.
    Last edited by HMS_Beagle; 07-20-2019 at 03:49 PM.

  9. #139
    tWebber lee_merrill's Avatar
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    Quote Originally Posted by HMS_Beagle View Post
    Exactly as expected Lee quote-mines and lies about the paper. BTW Dory the first link is the summary of the paper, the second is the paper itself.
    No, those are two different papers. And you didn't respond to my counterpoint, ad hominems are not a reply.

    Blessings,
    Lee
    "What I pray of you is, to keep your eye upon Him, for that is everything. Do you say, 'How am I to keep my eye on Him?' I reply, keep your eye off everything else, and you will soon see Him. All depends on the eye of faith being kept on Him. How simple it is!" (J.B. Stoney)

  10. #140
    tWebber HMS_Beagle's Avatar
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    Quote Originally Posted by lee_merrill View Post
    No, those are two different papers. And you didn't respond to my counterpoint, ad hominems are not a reply.
    Feel free to explain why you dishonestly quote-mined and lied about the overview article which gave three possible evolutionary pathways for ribozyme. You quote mined the first pathway which was described as extremely unlikely for more complex ribozymes and completely ignored the other two pathways which have supporting positive evidence.

    Nobody likes a liar Lee, especially God.

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