Lecture 5 - Proteins: Amino Acids and Structure

Biochemistry

protein

one type of biological polymers

large biological molecules consisting of one or more chains of amino acids

made up if one or multiple polypeptide chains

peptide

short chain of amino acid monomers linked by polypeptide bonds

amino acid

biologically important organic compound made from amine and carboxylic acid functional groups, along with a side chain specific to each amino acid

amine group - primary

pka 9-10

carboxyl group - alpha carbon

pka 1.5-2.5

Glycine (gly)

L-Alanine (ala)

L-Valine (Val)

L-Isoleucine (ileu)

L-Leucine (leu)

L-Serine (ser)

L-Theronine (thr)

L-Proline (pro)

L-Aspartic acid (asp)

L-Glutamic acid (glu)

L-Lysine (lys)

L-Arginine (arg)

L-Asparagine (asn)

L-Glutamine (gln)

L-Cystein (cys)

L-Methionine (met)

L-Tryptophan (trp)

L-Phenylalanine (phe)

L-Tyrosine (tyr)

L-Histidine (his)

acidic amino acids

asp & glu

basic amino acids

arg, his, & lys

neutral amino acids

ala, asn, cys, gln, gly, his, ile, leu, met, phe, pro, ser, thr, trp, tyr, val

alpha carbon chiral in all amino acids except for…

glycine

all natural amino acids are L or R form?

Left

L-Alanine

D-Alanine

L-Glyceraldehyde

D-Glyceraldehyde

characteristics of polar amino acids

neutral, basic, acidic

characteristics of non-polar amino acids

alkyl, branched, aromatics, unique

Acidic negatively charged R Polar Amino acids

Asp and Glu

Basic positively charged R Polar Amino Acids

Lys, Arg, His

Neutral Polar R no charge

ser, thr, tyr, asn, gln, cys

Alkyl non-polar amino acids

Gly, Ala

Branched chain non-polar amino acids

val, leu, ile

Aromatics non-polar amino acids

phe, trp

Thioether non-polar amino acid

met

Secondary Amine non-polar amino acid

Pro

Essential amino acids in humans

(only available in food)

Histidine, Isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine

Nonessential amino acids in humans

(can be synthesized in body)

Alanine, arginine, aspartic acid, asparagine, cysteine, glutamic acid, glutamine, glycine, proline, serine, __tyrosine__

Ketogenic amino acids

leucine, lysine (acetyl CoA, acetoacetyl CoA)

Glucogenic amino acids

glycine, serine, valine, histidine, arginine, cysteine, proline, alanine, glutamine, aspartate, asparagine, methionine (glycosis, gluconeogenics, krebs → sugar metabolism)

Both ketogenic and glucogenic

isoleucine, threonine, phenylalanine, tyrosine, tryptophan

zwitterion

have both negatively and positively charged groups but the overall charge in the molecules is 0

isoelectric point pI

the ph value at which the overall charge of zwitterion is exactly zero

if R group does not have dissociable groups: pI=(pK1+pK2)/2

if R group has dissociable group: pI=pK3/pKR

amine bond or peptide bond

covalent bond between amino group of one amino acid and alpha carboxyl group of another amino acid

dehydration reaction

energy dependent; GTP

In vivo formation of peptide bond

several proteins and a nucleic acid scaffold are involved; both protein type enzymes and ribozymes are involved

how much energy is needed to rotate a peptide bond?

88 kJ/mol

configuration at peptide bond

planar, trans configuration → undergo little rotation as it is restricted

a lot of energy is needed to break a peptide bond

True

Peptide bond partial double bond

N-terminal end

free unbounded amino group

C-terminal end

free unbounded carboxyl group

what is the difference of a peptide and a protein

peptides are short chains or less than 25 amino acids and can have biological properties: functional

proteins have more than 25 amino acids and have one biological polymer: macromolecules

what does protein structure determine

function, it sets the foundation for its interaction with other molecules

4 levels of hierarchy in protein structure

primary, secondary, tertiary, quaternary

3 main types of secondary protein structure

beta sheet

alpha helix: spiral chain

coil/loop and turn

(T or F) R groups determine amino acid water solubility (secondary protein structure)

T

which amino acid favors helix structure

glycine in collagen

which amino acids are helix breakers

proline

H bond and beta sheet does what

stabilizes this structure into a plated arrangement

Anti-parallel vs parallel beta sheets

protein motifs

recognize specific signal/ligand

interact with DNA gene promoter

interact with some other proteins

protein domains (motif/suer secondary structure)

perform a particular chemical or physical task/function

nuclear receptors

a class of proteins that are responsible for sensing steroid and thyroid hormones, xenobiotics, and certain other molecules. In response, these receptors work with other proteins to regulate the expression of specific genes, thereby controlling the development, homeostasis, and metabolism of the organism

what does a protein require for it to be functional

multiple individual function components

DNA binding domain (DBD)

an independently folded protein domain that contains at least one structural motif that recognizes double or single stranded DNA

hydrophobic effects

causing no interaction with water

hydrophobic core

major determinant of native protein structure

electrostatic interactions

mainly van der waals force (short distance)

disulfide bonds

between two cysteine

metal ions

ionic force (iron in heme, zinc fingers-DNA binding protein)

relationship of configuration/ 3D structure of a protein and its function

* correct configuration or 3-D structure of a protein is essential for its function


* alteration of configuration or 3-D structure of a protein leads to alteration of its function
* activation & inhibition

Strategies to alter protein configuration

1. protein-protein interaction → chaperone protein driven folding and refolding
2. ligand binding → activators and inhibitors
3. phosphorylation and acytylation

chaperone protein

the protein that assists the non-covalent folding or unfolding and the assembly or disassembly of other macromolecular structures, such as other proteins

GroEL

a bacteria protein that helps folding of newly synthesized proteins or misfolding proteins

hydrophobic inner hole

required for protein folding

hydrophilic surface

attracts misfolding proteins

binding protein

stabilized correctly folded protein

myoglobin (Mb) and Hemoglobin (Hb)

oxygen binding proteins in mammals

myoglobin (Mb)

monomer oxygen binding protein → tighly bound to one heme molecule

Hemoglobin (Hb)

tetramer oxygen binding proteins → 2 alpha and 2 beta chains. Bind to 4 heme molecules

myoglobin

a red protein containing heme that carries and stores oxygen in muscle cell

tetramer

2 alpha and 2 beta protomers/subunits → binding to 4 heme molecules

Bohr effects

hemoglobins oxygen binding affinity is inversely related both to acidity and to the concentration of carbon dioxide

what is the result of a decrease in blood ph or an increase in blood co2 concentration

hemoglobin proteins releasing their loads of oxygen → carbon dioxide reacts with water to form carbonic acid

what muscle does during exercise

generate lactate and more co2 generated

what does a decrease in carbon dioxide pressure or increase in ph

hemoglobin picking up more oxygen

transportation of O2 and CO2 between lung and tissues: carbonic anhydrase

CO2 pressure is higher in muscle than lungs which leads to

O2 binding to hemoglobin in lung but O2 released in muscle

Discuss why the oxygen will dissociate from hemoglobin or why more oxygen will be delivered to muscle in an active tissue, such as the muscle during physical exercise

* CO2 pressure is high
* Temperature is high
* lactate is generated
* blood shunt from liver to muscle

→ lowering pH

Bohr effect → left shift

more binding → less CO2 and higher pH

Bohr effect → right shift

less binding → more CO2 and pH