Serine proteases & inhibitors… Sometimes serine is serene - other times it’s sabotaging other proteins by providing the blade to “protein scissors” called serine proteases. That’s really not fair of me to characterize them in a bad light - you can’t blame these proteins for just doing their job. In the body they have lots of crucial jobs - serine proteases are involved in digestion, hormone activation, blood clotting, immune system activation, and much more - and serine’s not acting alone - in one of the most biochemically beautiful examples of atomic cooperation, it serves as part of a catalytic triad, getting help from histidine and aspartate. But it’s all about right place, right time!
blog form: http://bit.ly/serineserineproteases
It’s Day 20!!!!! of #20DaysOfAminoAcids - the bumbling biochemist’s version of an advent calendar. Amino acids are the building blocks of proteins. There are 20 (common) genetically-specified ones, each with a generic backbone with to allow for linking up through peptide bonds to form chains (polypeptides) that fold up into functional proteins, as well as unique side chains (aka “R groups” that stick off like charms from a charm bracelet). Each day I’m going to bring you the story of one of these “charms” - what we know about it and how we know about it, where it comes from, where it goes, and outstanding questions nobody knows.
More on amino acids in general here http://bit.ly/aminoacidstoproteins but the basic overview is: amino acids have generic “amino” (NH₃⁺/NH₂) & “carboxyl” (COOH/COO⁻) groups that let them link up together through peptide bonds (N links to C, H₂O lost, and the remaining “residual” parts are called residues). The reason for the “2 options” in parentheses is that these groups’ protonation state (how many protons (H⁺ ) they have) depends on the pH (which is a measure of how many free H⁺ are around to take).
Those generic parts are attached to a central “alpha carbon” (Ca), which is also attached to one of 20 unique side chains (“R groups”) which have different properties (big, small, hydrophilic (water-loving), hydrophobic (water-avoided), etc.) & proteins have different combos of them, so the proteins have different properties. And we can get a better appreciation and understanding of proteins if we look at those letters. So, today let’s look at Serine (Ser, S)
We’ve talked a lot about how our bodies can recycle amino acids and use them (or parts of them) to build new molecules - other amino acids and even other things like sugars & fats. But in order to recycle individual amino acids you have to “individualize” them - you need to cut up the big ole proteins into single letters and process them individually. This involves breaking up those super-sturdy peptide bonds linking up the amino acid letters. The key is to make them less stable and more irresistible to attackers.
Atoms (like individual C’s & O’s) are made up of smaller “subatomic particles” - positively-charged protons and neutral neutrons hang out together in a dense central core called the atomic nucleus. And negatively-charged electrons whizz around them in an “electron cloud.” Atoms join together to form molecules by sharing pairs of electrons. But they don’t always share fairly, so you can get partly positive parts of molecules and partly negative parts of molecules and we call this uneven charge distribution “polarity.” http://bit.ly/frizzandmolecularattrac...
The carbonyl C (carbon double-bonded to oxygen) is the most vulnerable to attack because, although it might not look like it, it’s partly positive because the O is hogging the electrons they’re sharing (we call such electron-hogs electronegative). Since the C is partly positive, and molecules don’t really like being charged, the C is happy to add some negativity if a positivity-seeker (nucleophile) comes along. (so we say this C is electrophilic, loving electrons). Since each atom can only form a limited number of bonds, you end up with some electron rearranging leading to the peptide bond being broken.
So you can break a peptide bond through nucleophilic attack - now we just need a strong nucleophile. If you deprotonate (remove a proton, H⁺ from) an alcohol (-OH) group you get -O⁻. This O is negative (fully this time because it has more electrons than protons, they’re not just unevenly distributed) and really nucleophilic (this means it wants some positivity, remember). That alcohol group can be part of water, but it doesn’t have to be - it can, for example, be sticking off of a protein in perfect position to attack…
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