Lecture 4 & 5 Bioinformatics & Proteins

Question 1

Is protein structure more highly conserved than its sequence? why?

Answer 1

yes it is

Question 2

define, homologs, paralogs, and orthologs

Answer 2

Very similar structure, Para, same specie diff. function, Ortho differ specie SAME function. ex. bovine ribonuclease and human ribonuclease - digestive enzymes.

Question 3

What is bioinformatics and how can it be useful?

Answer 3

think biological data, gene sequencing, amongst all life.

Question 4

similarities of AA mean they would have similar what?

Answer 4

Size, shape, polarity, structure.

Question 5

blosum 62 table is used for? and how read

Answer 5

A scoring system that detects homology between Protein sequences, and is used for comparing species or looking at how things have evolved/differentiated. Conserved and Non-conserved Substitutions.
0 or above (+) means they are similar structure is conserved, and <0, (-) neg, means structure is not conserved. ( you will not have to figure out the gaps)

Question 6

Blast analysis?

Answer 6

way to put in chains of AA and have read the similarities/differences.

Question 7

be able to define what your are looking for in blosum 62? we evaluate what? how is this defined and what numerical value?

Answer 7

CONSERVED SUBSTITUTIONS - similar AA.
62# - postive 0 and above.
NON conserved substitutions-dissimilar AA.= negative blossum 62

Question 8

Sliding aa analysis compares what and determines what?

Answer 8

compare 2 AA chains/sequences side by side to

identity regions of significant overlap or the lack thereof

Question 9

When comparing a sequence of A.A. residues amongst several different organisms to see how much the AA. residues can vary or have changed through time. what does tolerant, intolerant and hyper variability mean for the residues?

Answer 9

Intolerant residue in seq means it hasn’t changed over time and therefore Cannot withstand variability in A.A..
Tolerant = It has withstood some changes in, somewhat variable
Hyper variable = all residues can be different, highly variable

Question 10

describe the Alignment/scoring process for the 2 types of sequencing comparison techniques we learned?

Answer 10

Sliding and Shuffleing
Sliding - simply line up, and add the the identical a.a. with the conservative substitutions (from blosum 62) and divide by the total of aa.. you will have a percent of similarity and if its >40 then
shuffling - take original sliding, then mix all A.A. up and determine a new sliding score, if its similar then the alignments could simply be random

Question 11

1. describe secondary and tertiary structure. types of bonds/interactions, location of residues, structures formed?

Answer 11

Secondary - H bonds between 2 non adjacent AA residues. from the NH to the carbonyls oxygen. this forms, Alpha helices or Beta Strands. Multiple beta strands =B sheet
Tertiary, is multiple secondary structures coming together through Hydrophobic interactions b/w distant R-groups on the SAME polypeptide chain.

Question 12

how many degrees between each AA?

How many aa in one turn?

Answer 12

100degrees therefore also 100 degrees between each R group!!
3.6aa/turn.

Question 13

What type of reaction to form the peptide bond in primary structure? Whats released

Answer 13

dehydration

H2O

Question 14

another name for the peptide bond? and What is special about what this bond and molecule exhibits that reflects greatly on its structure and movement?

Answer 14

Amide bond
There is resonance in the Carboxyl to the amide bond which means it is essentially planar and rotation about this bond is prevented and conformation is constrained.

Question 15

why can polypeptides form tightly packed globular structures?

Answer 15

b/c the peptide bond is uncharged.

Question 16

R groups across Peptide bonds nearly always prefer what configuration? and the exception is?

Answer 16

Trans, due to steric clashes.

X-Pro linkages can be both, b/c both are sterically hindered.

Question 17

Where does rotation about a bond in the aa backbone occur?

Answer 17

The other 2 bonds of the amino Acid, the N-alpha Carbon, Phi bond
and Carbonyl C-alpha C, Psi bond.

Question 18

Ramachandran diagram tells us what?

Answer 18

Which of all the combinations of Torsion angles from Psi and Phi bonds are possible (ie sterics wont interfere)

Question 19

What does proline do to Alpha helices? and why?

Answer 19

Disrupts there configuration due to the lack of the H on the N terminus, b/c of the ring causing deprotonation.

Question 20

Beta strands are unlike an alpha helix in that they are? how many strands make up a sheet?

Answer 20

fully extended and therefore flattened and not compact.

2 or more strands for a sheet

Question 21

Essentially, all Alpha helices found in Proteins are ________ handed?

Answer 21

Right

Question 22

Hemeglobin is mostly what secondary structure? why?

Answer 22

Alpha Helices, b/c of its stability and the fact that Hemeglobin must be bombared with Oxygen and its ability to form radicals.
transmembrane proteins contain Alpha helices

Question 23

H bonding in a helix compared to a sheet is similar or different? how so?

Answer 23

Different, Sheets have H Bonding that is perpendicular to the plane of the sheet and Alpha helices have their H bonding parallel to the plane of the Alpha helices, ie not sticking out for the helix.THIS IS WHY THEY CALL SHEETS AND STRANDs sticky.

Question 24

Why are antibodies sticky and what happens in Alzheimers?

Answer 24

B sheets, due to there hanging H’s, are sticky. In Alzheimers, helices conformationally change to sheets and become sticky and the amyloid plaques can then form.

Question 25

how many AA residues make up a helix and strand respectively?

Answer 25

12
4-5
so sheets have at least 8 aa, and why is this so few.
the strands are stretch out to nearly 180 degree bond angles.

Question 26

the strands of sheets can run in different directions? what are these to formations called and whats different about there bonding?

Answer 26

Parallel and anti parallel
The parallel strands have hydrogen bonds that connect each aa in one strand to 2 different aa on the adjacent strand, and in anti parallel its one for one pairing.

Question 27

Polypeptide backbone is formed in what Direction? and what is repeating atom sequence of backbone?

Answer 27

N to C with N being the beginning and C the tail.

NCC NCC NCC NCC etc.

Question 28

on Beta Strand, what is the distance between consecutive R groups on one side of a sheet?

Answer 28

7A for every other, b/c its 3.5A between aa but the R groups alternate sides of the sheet.

Question 29

What 2 Fibrous proteins provide structural support for the cells and tissues?

Answer 29

Collagen and alpha Keratin.

Question 30

What does keratin consist of to form its general structure?
whats unique about keratins AA sequence?
where is it found in the body?

Answer 30

• 2 alpha helices intertwined to form a type of left handed.
• super helix called an Alpha helical COILED COIL
• Found in hair, skin, intermediate filaments, cytoskelton, myosin, tropomyosin

Question 31

Whats special about keratins sequence that helps it to for its tertiary structure

Answer 31

it has the HEPTAD REPEAT, imperfect repeat of 7 aa, but the 7th is always Leu.
the 2 helices are held together in the super coil by weak interactions such as van der waals and ionic interatctions between these Leu.
Also Disulfide bonds from neighboring cystein residues, may be formed to help stabilization.

Question 32

Keratin Heptad has how many residues per turn? and why

Answer 32

3.5 instead of the 3.6 seen in normal alpha helices. thus the pattern can be repeated every 7 residues forming the heptad repeats.

Question 33

Whats the most abundant protein in mammels?

what is this protein a component in?

Answer 33

Collagen

the main fibrous component of skin, bone, tendon, cartilage, and teeth

Question 34

what is collagens structure? in general and what residues make it what it is?

Answer 34

THREE helical polypeptide chains. With glycine appearing every third residue in the sequence, along with Proline, and Hydroxyproline.

Question 35

Is Collagens internal helical bonding similar to that of other alpha helices?
What about the bonding between the helices, is it like Keratin?

Answer 35

Its backwards to both
Alpha helices, do not have H bonding, but instead is stabilized by steric repulsion of the pyrrolidine rings of the proline and hydroxyproline residues.
The strands however, unlike keratin, are stabilized by H bonds.

Question 36

Why does Collagen have this repeating every 3 GLY residue structure?

Answer 36

The inside of the triple stranded helical cable that is held together by H bonding is very crowded and the only residue that can fit in an interior position is glycine. The other 2 large AA is located on the outside of the cable.
lose the glycine, get brittle bone disease,b/c the elasticity of this major component of bones is not flexible anymore with out the glycine.