Chem 489 - Test 1

Front 1

Single nucleotide polymorphisms(SNPs)

Back 1

can generate only a subset of amino acid changes

For example, a SNP can change Vto F, L, I, M, A, D, E or G. F, L, I, M and A would result in a conservativeamino acid change, while D, E and G would produce a significant change.

More common mutations aretransitions (a to g and g to a, or c to t and t to c) than transversions(a, g to t, c or t, c to a, g)

Front 2

Pitch

Back 2

The distance per turn

Front 3

N

Back 3

number of amino acids per helical turn

Front 4

D

Back 4

Distance between amino acids

Front 5

At what residue does N-H bonds to C=O

Back 5

N-4th

Front 6

Avg length of helix, pitch, and n

Back 6

~12 residues, 5.4 A, 3.6

Front 7

Helical Wheel

Back 7

The side chains of a helix are onthe outside, so they determine the surface properties of the helix. These properties can be readily seen in ahelical wheel. Placed every 100 degrees

Front 8

Helix Propensity

Back 8

The relative frequency at which the amino acids are found in helices

Front 9

Helix nomenclature

Back 9

n = # of resiues per turn and m is the number of atoms in the ring closed by the H-bond.

Front 10

2.2 7, 310, alpha, pi

Back 10

never seen (torsionally strained)

310 has steric interference

pi regions are too wide for van der Waals

Front 11

Polyproline II helix

Back 11

Left handed helix, proline at every third residue; important in cell signaling. SH3 domains

Front 12

Why are beta sheets pleated?

Back 12

psi and phi angles are somewhat less than 180 to minimize steric overlap and bonds are completely parallel. seperated side chains on same side by 7 A.

Front 13

Avg strands in beta sheets? width?

Back 13

6 strands; 25 A

Front 14

Why does a beta sheet have a rt handed twist

Back 14

Although H-bonds are decreased, the steric repulsion of side chains are also reduced. It is an energetic compromise.

Front 15

Where do you want to see disulfide bonds?

Back 15

Outside, inside of cell is highly reducing

Front 16

Phi and Psi

Back 16

Phi: alpha carbon & N

Psi: alpha carbon & C=O

Front 17

Typical angles: alpha helix, beta sheet

Back 17

From Ramachandran plot

Alpha: psi = -47 & phi = -57

Beta: psi = 113 & phi = -119

Front 18

Chi angles

Back 18

Side chain rotamers: defined by chi angles

Front 19

Why do we want some of these interactions to be weak?

Back 19

We need them to be reversible in most biological settings

Front 20

Where do the side chains of beta sheets project

Back 20

above and below

Front 21

In beta sheets, what is the arrow?

Back 21

The arrowhead is the C terminus and the other end is the N terminus

Front 22

Why are transition mutations more common than tranversion?

Back 22

A to G is much more likely than A to T because it's more likely to be conservative.

Front 23

What is a loop region?

Back 23

Between alpha helix and beta sheets are loop regions. Often exposed to surface

Front 24

Why are AA changes found most often in loop regions?

Back 24

Doesn't affect the function of the protein (usually)

Front 25

Types of Loops between Beta sheet

Back 25

B turn is common

Right handed crossover is very common

Left handed crossover is uncommon

Front 26

What amino acids are involved in hairpin loops

Back 26

Proline and Glycine

Front 27

Describe omega loop

Back 27

found in almost all proteins with 60+ residues, they are 6-16 residues in length. Important for binding sites; Their termini are < 10 A apart giving an omega look

Front 28

Average Tertiary Structures

Back 28

31% alpha, 28% beta, 31% loops, rest unstructured

Front 29

What is the strongest molecular force that drives protein folding?

Back 29

Hydrophobic forces; about 3KJ/mol decrease in delta G when a CH2 group is removed from water

Front 30

Why does entropy increase?

Back 30

Because water forms ordered structures around non-polar molecules

Front 31

U=kqq/Dr

Back 31

U is the energy required to separate two charges

q1 and q2 are the two point charges.

(a full ionic charge is 1.60x10^-19C)

k is 9.0x10^9 Jm/C^2

r is the distance between charges

D is the dielectric constant of milieu

Front 32

Ion pairs:

Back 32

Contribute little to free energy and actually decreases entropy because they can ineract with water

Front 33

pi cation interactions

Back 33

delocalized electrons of aromatic rings interact with cations; usually occur between Trp, Tyr, or Phe with Arg or Lys.

Front 34

Nicotine forms a______ with ACh receptors in brain.

Back 34

pi cation interactions

Front 35

Why aren't H-bonds more stable than 40KJ/mol

Back 35

Most aren't ideal. they compete with H-bonds of water. Many H-bonds are not at 180, but still contribute a lot of stabilization energy to protein folds. Proteins also have many destabilizing forces which counter

Front 36

What destabilizes a protein's fold?

Back 36

Entropy decreases, van de Waals overlap (sterics), and electrostatic repulsion

Front 37

Motif

Back 37

A super-secondary structure that becomes part of the tertiary structure

Front 38

Types of Motifs

Back 38

Helix-loop-helix

Isolated hairpin

Hairpins as part of an anti parallel B-sheet

The Greek Key - antiparallel sheets - 1 and 2 are sandwiched by 3 and 4

Beta alpha beta motif (beta are parallel)

Alpha alpha

Front 39

Alpha domains

Back 39

The four helix bundle

Seven helical bundle

Coil Coil alpha domain ( left handed manner; # of residues decreases to about ~3.5)

Collagen Triple helix - Ascrobic acid is used to make hydroxyprolines; there is a Gly at every third residue

Front 40

Beta Domains

Back 40

Beta Sandwich - most common

The up-and-down beta barrel

Greek Key Beta barrel

Beta Propeller

Front 41

Alpha Beta Domains

Back 41

The alpha beta barrel - eight helices suround eigh stranded parallel beta barrels ( almost always enzymes)

Open Beta Sheets (Beta alpha beta)

Front 42

Where do we find the active site in beta sheet domains?

Back 42

Almost always found in the crevice created from the crossover point at the C-terminus of the beta sheets. Mostly in the loops after the Beta strands

Front 43

Why do domains sometimes fold dependently on another domain?

Back 43

Sometimes they need the other for stability

Front 44

Quaternary structure?

Back 44

The association of polypeptides in order to provide physiological function.

Front 45

Oligomer

Back 45

A protein complex made up up protomers (subunits). Can be hetero or homo. (most are homo) Two subunits is a dimer... etc

Front 46

If a homo-oligomer has the same function as the protomer alone, why bother?

Back 46

Increased size could mean increased stability of active site, making it more catalytically convenient.

Front 47

Tightly bound complexes do what compared to weakly bond complexes?

Back 47

Have more hydrophobic interactions

Front 48

Symmetry!

Back 48

Cyclic symmetry - subunits can be brought into coincidence by single axis of rotation; Cn symmetry = 360/n (ex: C4 = 90 degree rotation)

Front 49

Dihedral Symmetry

Back 49

Subunits can be brought into coincidence by n fold rotation around one axis and a two fold rotation along a second perpendicular axis.

Front 50

How are complexes determined?

Back 50

Affinity purification methods are used to isolate complexes - Immunochemical, One step affinity purification, two step affinity purification

Mass spec can also be used

Cross-linking (Dimethylsuberimidate or Glutaraldehyde)