PyrRolysine - NOT pyro-lysine - it’s lysine with a pyrrole group, not lysine on fire! Though its discovery as the 22th genetically-encoded proteinogenic amino acid (protein letter) set the scientific community aflame in 2002! I got away with not mentioning it before because it isn’t found in humans - or even mice or flies - it’s only found in a few bacteria and archaea, who use it to help break down carbon-y things into methane (which humans can potentially use as an alternative energy source). And they’re able to use this special amino acid by rewriting their genetic code slightly so that this special protein letter replaces one of the protein-making stop signs, UAG (there were 3 already, so they won’t miss one!) This lets them introduce this “unusual” 22nd amino acid into their proteins (and scientists are using this “orthogonal” strategy to introduce unusual amino acids into other proteins in the lab).
blog form: [ Ссылка ]
Proteins (molecular machines) are made up up of chains of building block “letters” called amino acids that are like charm bracelets. Amino acids have a generic backbone (chain link) that allows any amino acid to connect to any other amino acid as well as a unique side chain “charm” that sticks out. Charms have different chemical properties that allow them to interact in different ways w/one another (important for the protein to fold properly) & w/other molecules (important for intracellular interactions).
Over the past few weeks, we saw the 20 “usual” amino acid charms. And then I introduced you the the 21st, selenocysteine (Sec) which has a “-CH₂-SeH” charm and, as we’ll talk more about later, it sometimes gets cells to bypass the UGA stop sign. Sec was discovered in the 1970s. And scientists were really surprised. And then in 2002, they were hit again - a 22nd amino acid was discovered! And it was found by scientists studying some weird little organisms called archaea.
Archaea are a weird evolutionary branch that have some things in common with bacteria and other prokaryotes (like being single-celled and not having membrane-bound rooms called organelles (like nuclei for DNA storage/protection & mitochondria for energy production)). But they have other things in common with “eukaryotes” - things like plants, people, pigs, and more that do have such organelles.
There’s a LOT we don’t know about archaea - in part because we probably haven’t found the vast majority of them - many of them are “extremophiles” - they can live in places that are really hot, really cold, really salty, etc - basically extremophiles are organisms that have been able to specialize and carve out their own niche where no one can (or at least no one wants to) live - no competition, yay! Some archaea are “methanogenic” - methanogens can degrade organic (carbon-based) matter that’s hard for others to breakdown, like lipid breakdown products, into methane (CH₄). But they don’t break down the methane, so humans can use it as an alternative energy source. Methanogenesis makes energy for them - and for us! Even better, they tend to live places other things don’t want to - places with little available oxygen (anaerobic environments) such as marine & freshwater sediments - even in municipal waste digesters.
So they make attractive study subjects - we’ll discuss more about the discovery later but first I want to tell you about how this amino acid sneaks in there… So scientists were studying some of the protein enzymes that these critters use to mediate & speed up their methane-making - and they found these enzymes had modified amino acids. That part wasn’t that weird. Amino acids are known to be modified - some of them (like serine, threonine, & tyrosine) can get phosphorylated (have negatively-charged phosphate (PO₄) groups added on); others (like arginine) can have sugar chains attached through “glycosylation,” etc. But those modifications are added *after* the fact - after the protein is made (translated) - thus we call them post-translational modifications.
In this case, the modification was the addition of a pyrroline group onto lysine - that’s a 5-sided ring where one of the “corners” is a nitrogen, the other four are carbons, and there’s one double bond (more on this later). The weird part about these pyrrolysines was that these modifications were happening *before* the letter was even added - the protein-making machinery (a protein/RNA complex called the ribosome) was adding it directly to the growing peptide chain (which would fold up to become a functional protein). And to understand why this is *really* weird you have to have a general idea about how translation works.
finished in comments
