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Protein Processing 10711
UC MED 2015
24
Medical
Graduate
10/12/2011

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Term
How are enzymes targeted to lysosomes?
Definition
N-linked oligosaccharide Mannose-6-phosphate
Term
This is the enzyme that transfers GlcNAc phosphate from UDP-GlcNAc to an enzyme destined for the lysosome.
Definition
N-acetyl-glucosamine (GlcNAc) phosphotransferase
Term
What protein removes GlcNAc from a protein that will have the M-6-p N tail?
Definition
phosphodiesterase
Term
What ensures lysosomal enzymes targeted to
vesicles that are ultimately directed to the lysosomes? Where are they found?
Definition
Mannose-6-phosphate receptor

They are found on the lumenal trans golgi, also some are found on the external plasma membrane (life isn't perfect some are accidentally secreted)
Term
What causes the phosphorylated enzyme to dissociate from its receptor, and the receptor recycles back to the Golgi?
Definition
low pH of the clathrin sorting vesicle
Term
What simple test can be done to determine if a person has I-cell disease?
Definition
Blood test, will see 10 to 20 fold increase of of hexosaminidase, iduronate sulfatase, and aryl sulfatase A activity in serum. These enzymes are suppose to be in the lysosome
Term
Proteins that are secreted from the cell are more likely to have __________ for extra stability?
Definition
disulfide bonds
Term
As insulin is processed in the golgi, it can bind which inorganic molecule?
Definition
zinc
Term
How many insulin molecules come together to bind zinc?
Definition
6 (hexamer) known as zinc insulin crystals
Term
What is another name for insulin in the hexameric form?
Definition
lente insulin
Term
Lente and ultralente insulin depend on changes in the ______________.
Definition
Quaternary structure
Term
Analogues of insulin depend on changes in the ___________.
Definition
primary structure
Term
In lispro insulin, what is the change that has been induced and what does it do and how does lispro differ?
Definition
In the C- terminus flip Lys-Pro-Tyr to Pro-Lys-Tyr.
This disrupts the beta sheet that will form here. the beat sheet. holds the dimeric insulin together.
Now its fast acting insulin.
Term
If insulin can't form dimers its even less likely to form...
Definition
hexamers
Term
T and R states of insulin are associated with ligand binding to 2 allosteric binding sites, they are...
Definition
phenolic pocket and the His B10 Zn2+ anion site
Term
What binds in one of the allosteric sites of insulin, stabilizing the R form of hexameric insulin and creating ultralente (long lasting insulin-duration of action is long lasting).
Definition
methylparaben
Term
The last 9 residues of the B-chain of insulin go from________ to __________, when going from the T state to the R state.
Definition
these residues go from an extended conformation in the T-state to an α-helical conformation in the R-state
Term
the term Rf in T3R3f denotes “frayed” where
Definition
residues B1–B3 are found in a non-helical conformation
Term
Does the T or R form of insulin have the phenolic pocket?
Definition
R form- note this pocket is hydrophobic
Term
Helix side chains making up the lining of the tunnel in the R form are>
Definition
Phe B1, Asn B3, and LeuB6
Term
Zinc is coordinated to _______ at the botom of the tunnel in the R form of insulin
Definition
3 His
Term
Low pH favors the __ form of insulin?
Definition
R form
Term
in the T3R3 conformation MPO binds to...
Definition
the phenolic pocket created by the movement of Phe B1
Term
In the T6 conformation MPO binds at
Definition
dimer-dimer interfaces of the T6 hexamer via interacting amino acids Leu A13, Tyr A14, Glu A17
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