proteins and AA's structure, nomenclature, properties

proteins are involved in

every cellular process

what are the functions for proteins (8)

• Enzymes

• Transcription factors

• Binding proteins

• Transmembrane proteins

• Hormones

• Immunoglobulins (key to our immune system; help kill foreign invaders)

• Signaling molecules (ex: insulin)

• Structural proteins (ex: collagen)

amino acids are linked via

peptide bonds

amino acids are the building blocks of

polypeptides and proteins

proteins make up how much of human dry mass

½

what are the common components of AA

• carboxyl group

• amino group

• chiral carbon

• Hydrogen group

• side chain (R group)

chiral center allows for

optical properties

related to stereochemistry

what AA does not have chiral central carbon?

glycine

has 2 H functional groups

how many AA’s are there

20

amino acids are characterized by their

side chains

all amino acids are in what formation?

L formation

what are the 20 amino acids (names)

• alanine

• valine

• leucine

• isoleucine

• lysine

• glycine

• phenylalanine

• serine

• proline

• cysteine

• glutamine

• asparagine

• arginine

• glutamate

• aspartate

• threonine

• methionine

• tryptophan

• tyrosine

• histidine

which are the essential AA’s (9)

• valine- Val

• leucine - Leu

• isoleucine - Ile

• phenylalanine- phe

• methionine- Met

• histidine- His

• Threonine- Thr

• tryptophan- Trp

• lysine- Lys

what are the nonessential amino acids (11)

• alanine- Ala

• glycine- Gly

• arginine- arg

• serine- Ser

• cysteine- Cys

• Proline- pro

• asparagine- Asn

• glutamine- gln

• aspartate- asp

• glutamate- Glu

• Tyrosine- tyr

what are the branched chain amino acids

valine (val), leucine (leu), isoleucine (ile)

which are the aromatic amino acids

• phenylalanine (phe)

• tyrosine (tyr)

• tryptophan (trp)

which amino acids contain sulfur

cysteine and selenocysteine*

the side chain of amino acids is important why?

• make side differences amongst AA's and give them their specific characteristics

•  differ by shape, size, chemical and physical properties

what can occur to proteins post-traslationally?

chemical changes through addition of carb, lipid, protein, chemical group to the specific amino acid side chain

the optical activity of an amino acids comes from what?

chiral center (α-carbon)

what amino acids lack optical activity?

glycine (does not have chiral carbon)

what are stereoisomers?

mirror images of each other

amino acids can are present as what 2 formations?

L or D

L formation of amino acid means what?

amino group is on the left

D formation of amino acid means what?

amino group will be on right side

which is the formation of all proteins and peptides in humans

L-formation

amino acids have what property?

acid-base properties

how do amino acids have acid-base properties?

Can function as a buffer when added to a solution (which could be acidic or basic in nature)

what is titration (AAs)

ab method where you slowly add a strong acid or base to amino acid solution and measure how the pH changes

what is a titration curve?

a graphical representation of the pH of a solution in a titratio

titration curve y and x axis?

• Y axis is the pH

• X axis is the moles of OH per mole of AA

the more basic, the more moles of OH per mole of AA

what is pKa

is the pH which the protonated and unprotonated groups are present in equimolar amounts

define protonated

 amino acid functional group has gained an H+

define deprotonated

amino acid functional group has lost an H+

which functional groups can be protonated/deprotonated in amino acid?

 amine group, carboxyl group, and/or R group (side chain)

what is the isoelectric point (pI)?

the pH at which the average charge on the molecule is zero (when at zwitterion)

titration of histidine explained

• Start with histidine at a net charge of +2 (fully protonated) and a pH 0

• At pka1 (1.82), we have a 1:1 ratio of histidine (+2) and histidine (+1)

• At pKa2 (6), we have a 1:1 ratio of histidine (+1) and histidine (0)

• At pKa3 (9.17), we have a 1:1 ratio of histidine (0) and histidine (-1)

• Becomes more basic because histidine loses its H's (to form water with OH group)

  • 1st to be removed in the COOH ----> becomes COO- (+1)

  • 2nd is the H from its functional group which includes NH+ --> becomes N (0)

  • 3rd is the H from the amine group (NH3+) --> NH2 (-1)

nonpolar amino acids will be incorporated into what area of the membrane

nonpolar

Aka, hydrophobic proteins reigns reside in lipid bilayer of the membrane

hydrophillic amino acids will be where on the membrane?

 outside of the membrane

Aka in the aqueous solution (polar)

what determines whether AA is hydrophobic or hydrophilic?

 the R groups of the amino acid

what is a major force in folding of proteins?

Hydrophobicity/Philicity

what is post-translational modification?

 when an AA can be modified by altering the R group

post-translational modifications of AA can occur _______ or ________

enzymatically or nonenzymatically

post-translational modifications of AA reversibility?

Can be reversive or irreversible

what do post-translation modifications do?

changes properties of the side chains and gives them a specific function

what are 5 examples of AA that have been modified post-translation?

• trimethyllysine

• methyllysine

• acetylcholine

• hydroxylysine

• gamma-carboxyglutamate

hydroxylysine function

• post-translation modification

• effects (2)

-hydroxylated via lysyl hydroxylase

-effects:

• allows chromatin to go through transcription

• help in the maturation of collagen

carboxyglutamate

• post-translation modification

• effects

• gains carboxyl group (a - charge)

• can now have calcium (2+) bind to it which will help in the blood cascade by stabilizing the charges (Helps stabilize the 2 negative charges (2 COO- groups) since it is Ca2+)

citrulline and ornithine play a role in the

urea cycle

homocysteine is important to

folate cycle

y-Aminobutyric acid (GABA) is what?

a neurotransmitter

what is a peptide bond?

 bond that forms when combining the carboxyl end on one amino acid with the amino end of another (C-N bond) and removing a water molecule

peptide bond looks how (letters)

C-N

a peptide bond is what type of bond

amide bond

peptide bond forms via what reaction

condensation

peptide bond is an ______ reaction

endergonic reaction

what is an endergonic reaction

reaction that requires energy input and will do by coupling to another reaction to get that energy

absorbs energy from surroundings

what is a peptide

30 amino acid residues or less linked togetherw

what is a polypeptide

 several amino acids linked together but does not have a defined confirmation of structure

what is a protein

 stable molecule that is in a specific 3D conformation

how does a peptide bond form (like what is it)

Between the carbon of the carboxylic group (C-terminus) and the Nitrogen on the amino group (N-terminus)

what is a key characteristic of a peptide bond

it is very stable and does not allow for rotation (acts like a double bond)

why does a peptide bond act like a double bond

the length is shorter than a normal single bond and slightly bigger than a double bond, so these forces give it greater stability

peptide backbone rotations

Rotation in peptide backbone occurs (C-C and N-C bonds) but NOT the C-N (peptide) bonds

peptide backbone rotations depend of

the R group (charge, size, hydrophobic or philic)

when naming a polypeptide, what order do you name it?

start with N-terminus and end with C-terminus

in this class we will name polypeptides using what name?

3-letter abbreviations for amino acids

how do you know where a amino acid ends on a chain?

Amino acids end at the C-N bonds

how do you know how many peptide bonds are in a polypeptide

# of AA’s - 1

what are 3 examples of common polypeptides?

• glucagon

• neuropeptides

• antidiuretic hormone (ADH)

polypeptides often need to be _________ to become active

altered

how are polypeptides often altered to become active?

via  cleavage or hydrolysis

what is a zymogen

inactive protein that needs to be activated via cleavage

seen in many vitamins and enzymes

what was one of the first proteins to be sequenced?

insulin

how does insulin become active?

insulin exists as preproinsulin (110 residues) —→ modified and becomes proinsulin (86 residues) —> modified and becomes insulin (51 residues)

what is the structure of insulin (components)

• made up of 2 polypeptides attached via 2 disulfide bridges

• alpha chain has 21 AAs and beta chain has 30 AA’s

stability of disulfide bonds

are very stable covalent bonds

what is the genetic code?

used to sequence out amino acids which ultimately get incorporated into proteins

how are proteins built? (starting with genetic code)

• DNA is transcribed into mRNA

  • DNA has 4 deoxyribonucleotides: cytosine, guanine, adenine, thymine

  • mRNA Contains 4 ribonucleotides: cytosine, guanine, uracil, thymine

• mRNA leaved nucleus and goes into cytoplasm

• mRNA code is carried to tRNA anticodons (3 letter)

• the tRNA anticodons have corresponding amino acids attach

• Continues process until it forms the polypeptide and then the protein

what is a single-point mutation?

A base letter could be swapped, added, or deleted which could result in the coding for a different AA

what is the result of a single point mutation?

Can alter structure or function of protein, stop the protein from being products, prevent the production entirely

example of a single point mutation?

PKU (phenylketonuria)

what is PKU

• what is it

• diet needed

• A genetic mutation that can be caused by a single-point mutation where one does not have the conversion of Phe --> Tyr

  • Phenylalanine hydroxylase is missing or defective (due to mutation)

  • Results in buildup of Phe

• Must consume a low Phe diet + Tyr added to diet

PKU is the disease that prevents the conversion of what amino acid from becoming what?

phenylalanine conversion to tyrosine

what is primary structure

specific, linear sequence of amino acids that make up the polypeptide chain (so order of AA on the chain)

primary structure directs what

 the folding of the protein into the 3D shape to make it functional

small sequences on the primary structure can do what(4)

• act as signals

• determine where protein goes (protein trafficking)

• determine where protein is inserted into the membrane

• allow for additional protein modifications that will impact biological regulation

what is secondary structure?

3D folding related to the hydrogen bonds that occur on the backbone

what are the 2 types of secondary structure?

alpha helixes and beta sheets

what is an alpha helix?

coiled secondary structure created by H bonds within backbone

in alpha helixes, where do R groups go?

project outwards

the alpha helix shape is held together via

H bonds

O from carboxyl and H from amine group (O-H)

what are beta sheets?

 folded/zizag pattern formed formed via H bonds

some side chains will do what that contributes to the formation of beta sheets?

somewhat restrict rotation

what are the 2 types of beta sheets?

parallel and antiparallel

what are antiparallel beta sheets

2 parts of the peptide chain are going in opposite directions which results in a perfectly lined up hydrogen bonds between amino group (H) attaches to carboxyl group (O)

stability of antiparallel beta sheets

very stable because the hydrogen bond is linear due to the O and H lining up

what are parallel beta sheets

beta sheets that form via “bent” hydrogen bonds when strands are running in the same direction

strength of parallel beta sheet

weaker because the O and H do not line up, so the H bonds is “bent”

tertiary and quaternary structures are both

functional