Serine Protease

enzymes are _____ that sustain life

catalytic enzymes

are propteins stable

yes they are very stable

what is the half life of a protein

37 C pH: 7.0 10-100 years

enzymes that catalyze the hydrolysis of the peptide backbone are

proteases

what do porteases do

shorten the half life of proteins to the millisecond time scale during many biological functions

where does thr stability of proteins come from

has a partial double bond character which strengthens the C-N bond and lowers the eletcrophilicity of the carbonyl carbon

how does proteases accelerate the hydrolysis of the peeptide bond

1. activating a nucleophile for a nucleophile substitution

2. polarizing oxygen of the carbonyl to increase the electrophilicity of the carbonyl carbon

3. stabilizing the tetrahedral intermediate

serine proteases are a class of

proteolytic enzymes

what do protelytic enzymes require

an active site serine residue for covalent catalysis

what are the three proteases

trypsin

chymotrypsin

elastase

____ is a crucial enzyme in the blood clotting casdcade

thrmbin

_____ is essential to dissolve blood clots

plasmin

____ is a bacterial protease

subtilisin

______ is a serine esterase related to serine protease

acetyl cholinesterase

where are chymotrypsin, trypsin, and elastase synthesized

in the pancreas and secreetd into the small intestines

What does chymotrypsin do

cleaves protein and peptides on the C-side of the aromatic resides

what does trypsin do

cleasves proteins and peeptides on the C-side of ARG or Lys resides

what does elastase do

cleaves peptides on the C-side of the small nopolar residues like gly, ala, val, and ser

where do the 3 proteases work together in

in the duodenum and form a potent digestive team

in chymotrypsin only ____ serine reacts with DIPF and result in complete inactive enzyme

serine

are the 3-D structures of the 3 proteases similar?

yes

how are the strutures folded

folded up into two domains both which have extensiv regions of antiparallel beta sheets and betas barrel like arrangements

where has His-57 and Ser-195 located

in the substrate binding pocket with an invariant aspartate residue Asp-102

what are His-57, Ser-195, Asp-102 called

catalytic triad

what does the aspartic acid do to the proteases

burying the hydrophobic solvent inaccessible pocket

all three of the catalytic trad residues are ____ bondded with each other

hydrogen

pancreatic trypsin inihibitior

protects the apncreas from self digestion by prematurely avtivated trypsin

the peptide bond in bocine pancreatic trypsin is between Lys-9151 and Ala-161 is posisitoned as if it were a

scissile bond

the carbonyl oxygen for. stwo hydorgen bonds with backbone amide hydorgens of Gly-193 and Ser-195

Oxyanion hole

what does the hydrogen bond in the oxyanion hole allow it to do

allow the enzyme to bind the tetrahedral intermediate in prefereance to either the enzyme substrate copmlex

manye nzymes are biosynthesized as larger inactive precursors known as

zymogens

how to zymogens become active

until they undergo specific proteolyic cleavage of one or several peptide bonds

zymogen activation is

irreversible process and exploited by biological systems to switch on and off

zymogens that are enzymes precursors are called

proenzymes

the precursor of trypsin is

trypsinogen

zymogen precursor of chymotrypsin is

chymotrypsinogen

zymogen precursor of elastase

proelstase

do the proteolytic zymogens have any power

no they dont have any catalytic power

the formation of blood clots is the result of. a

cascade of zymogen activation

seven blood factors are are serine proteases

kallikrein

XIIa

XIa

IXa

thrombin

is instigated when the blood comes in contact with an abnormal surface caused by injury

intrinsic pathway

initiated by factors released from injured sites

extrinsic pathway q

thrmobonin converts fibrinogen into

fibrin