Post translational modifications Flashcards by Andrew Pruett

O2, H202/ OH radical target what residues?

What is this called?

Cys/Met

free radical oxidation

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Carbonyls/aldehydes/ketones —> targets?

glycation

Lys/Arg/Cys
His

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NO—> ?

?’s targets

what is this called?

ONOO-, NO2

nitration

Tyr

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HS2–> ?

?’s targets

What is this called?

HS-

sulfhydration

cys

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Succination –>

fumerate (-OOC-C=C-COO)

Cys

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Phosphorylation —>

Donor group (DG) 
Target (TG)

DG: ATP
TG: Ser, Thr, Tyr

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Acetylation —>
DG
TG

DG: Acetyl Co-A
TG: Lys-Argq

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Methylation —>
DG
TG

DG: SAM
TG: Lys-Arg-His

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ADP-ribosylation
DG
TG

DG: NAD+
TG: Arg-Glu-Asp

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Glycosylation
DG
TG

UDP
DG: N-lingages, ASP
DG-: O-linkages (Set/Thr/Tyr)

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Small molecule modifications (glycosylation)

Lys–> OH-Lys
Pro–> OH-Pro

THEN glycosylation occurs at these hydroxyl sites

collagen molecules

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Myristoylatiln
DG
TG

DG: Co-A
TG: N-terminal Glu

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Palmitaylation
DG
TG

DG: Co-A
TG: Cys

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Farnesylation
DG
TG

…also known as

DG: Co-A
TG: Cys

prenylation

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Ubiquination

DG: ubiquinone
TG: Lys

degradation

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Sumoylation
DG
TG

DG: SUMO
TG: Lys

translocation and gene expression

small unbiquitine like modifier

proteins that get tagged on to other proteins

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ISG
DG
TG

DG: ISG
TG Lys

gene expression and translocation

interferron stimulated gene (product)

proteins that get tagged on to other proteins

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Oxidation: what does it do? With what? Targets?

Modifies proteins

O2- superoxide radical
H2O2/OH– hydrogen peroxide —> hydroxyl radical

His/Cys/Met/Tyr/Thr

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Glycation: what does it do? With what? Targets?

Modifies proteins
Carbonyls (aldehydes/ketones)

Targets: lys, arg, cys

irreversible

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ROS groups include

oxidation and glycation

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NOS groups

nitration (tyr) and nitrosylation (cys)

ONOO, NO

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Death Cascade involving GAPDH steps

GAPDH is a glycolytic enzyme

translocation
dna repair
apoptosis
telomere maintenance

modifications of GAPDH

N-acetylation

lys-117, 226, 251

modifications of GAPDH

s-nitrosylation

cys-152 modified

Modifications of GAPDH O-GlcNacylation

Thr-229

What do modifications to GAPDH do?

Modifications promote susceptibility of GAPDH to translocating into the nucleus to be destroyed

Protein Oligomerization Stable tetramer metastable dimer unstable dimer unstable chain Which of these is translocated into the nucleus?

the metastable dimer form

What causes GAPDH to be translocated into the nucleus?

GAPDH is a glycolytic enzyme in the glycolysis pathway | While doing it's job, something happens to injure the cell

Describe pathway to apoptosis

GAPDH (glycolytic) --> cell injury causes modification (acetylation, glycolation, nitrosylation) --> instability of enzyme --> GAPDH translocated into nucleus --> apoptosis

E1, E2, E3 enzymes involved in what?

ISG/SUMOLATION/UBIQUINATION E1 = activation of small protein (such as ubiquitone) E2 = transfer event (temporarily) E 3= ligation (small protein is attached to target)

SUMOLATION/ISG degradation or other?

other, such as gene expression

GAPDG signals the cascade leading to apoptosis

O-Glc-Nacylation targeting Thr-229 S-nitrosylation targeting Cys- 152 N-acetylation targeting Lys 117, 227, and 251

NMDA receptos do what

cells that excite neuron

Siah1

E3 ubiquination ligase responsible for translocating modified GAPDH into cell

Sulfhydryl Oxidation of GAPDH occurs at

Cys 152

Thr-229

O-GlcNacylation

Cys-152

s-nitrosylation

Lys-117, 227, 251

N-acetylation

s-thiolation occurs where

Cys-152

thiol--> sulfenic acid --> sulinic acid --> sulfonic acid --> what is this?

--> destroyed levels of oxidation

thiolation of Cys-152 does what, how?

protects it by inactivating it. the protein with the cys-152 is inactive. group can reversible thiolated/recovered

Tdh is the

yeast equivalent of GAPDH

Under basal levels of oxidation, tdh3 is

kept s-thiolated to protect it

high levels of oxidative stress do what to tdh?

tdh2 becomes inactivated due to chemical modifications

in what state is tdh3 maintained most of the time? tdh2?

tdh3 is glutathionated (inactivated) | tdh2 is active

What happens under intense oxidation in terms of tdh2 and 3?

tdh3 is thiolated and protected but tdh2 isn't. under immense oxidative stress tdh2 is destroyed. the tdh3 can then be converted into the active form rapidly

How do cells compensate for high oxidative stress?

tdh2 (active) becomes inactivated due to chemical modifications, so tdh3 (inactive) is converted into the activated form

how is tdh3 activated?

the glutathione is cleaved

Tdh3-glutathione vs Tdh3

inactivated to activated

where does the tdh3 activation occur as an example?

in neurons

how is hydrogen sulfide derived?

enzymatically from metabolism in pathways in cells

free radical oxygen targets

cys/met

Nitrosylation ?

exactly the same thing as nitration NO--> ONOO, NO2 cys