non-ser protease mechanisms

acid, base, nu for ser, cys, aspo, and metallo proteases
x = there isn’t one

ser: asp, his, ser
cys: x, his, cys
asp: asp, asp, water
metallo: x, Zn2+ and glu, water

aps protease mech

1. activate the nu (water) with one asp acting as base to extract proton from water
2. activated nu attacks the carbonyl C in the peptide bond
3. tetrahedral intmd is formed and stabilized by h bonding with a second asp
4. intmd rearranges, steals H back from the base asp and is released as 2 pdcts

hiv protease

cleaves the long strong of aa into segments that fold into viral proteins
only present in hiv and necessary for immature hiv to dev into mature hiv, so inhibitors designed to block the protease

why do asp protease release one pdct

the nu is water so when the tetrahedral intmd is formed, its not linked to the e and can leave - so it does after rearranging itself

cys protease

found in papaya and pineapple, hepatitis c uses cys protease to gen its proteins

cys protease mech

1. SH (thiol) in cys r group dets deprot bc adj his to become activated nu
2. it attacks the substr carbonyl to form the tetrahedral intmd
3. the first pdct is released with an N terminus (c terminus stays linked bc of thioester bond)
4. water comes in and is activated to be the second nu, hydrolyzing the thioester bond and releasing the remaining polypeptide

metallo protease

specific one is aminopeptidase, cleaves n terminal aa, basically docks at the n terminus and chews back a pp chain into aa

metallo protease mechanism

1. 3 aa form 3 coordination bonds with divalent Zn metal ion to hold it in place, then it bonds with water
2. substr binds and glu becomes basic, then yoinks a proton from water to activate the nu (zn2+ stabilizes the nu-oh and polarizes the carbonyl in the substr to inc el)
3. oh- attacks carbonyl c and forms tetrahedral intmd, stabilized by neighboring side chains and the Zn
4. the tetrahedral intmd collapses and releases the pdct