Lecture 4 & 5 Bioinformatics & Proteins Flashcards
Is protein structure more highly conserved than its sequence? why?
yes it is
define, homologs, paralogs, and orthologs
Very similar structure, Para, same specie diff. function, Ortho differ specie SAME function. ex. bovine ribonuclease and human ribonuclease - digestive enzymes.
What is bioinformatics and how can it be useful?
think biological data, gene sequencing, amongst all life.
similarities of AA mean they would have similar what?
Size, shape, polarity, structure.
blosum 62 table is used for? and how read
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)
Blast analysis?
way to put in chains of AA and have read the similarities/differences.
be able to define what your are looking for in blosum 62? we evaluate what? how is this defined and what numerical value?
CONSERVED SUBSTITUTIONS - similar AA.
62# - postive 0 and above.
NON conserved substitutions-dissimilar AA.= negative blossum 62
Sliding aa analysis compares what and determines what?
compare 2 AA chains/sequences side by side to
identity regions of significant overlap or the lack thereof
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?
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
describe the Alignment/scoring process for the 2 types of sequencing comparison techniques we learned?
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
- describe secondary and tertiary structure. types of bonds/interactions, location of residues, structures formed?
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.
how many degrees between each AA?
How many aa in one turn?
100degrees therefore also 100 degrees between each R group!!
3.6aa/turn.
What type of reaction to form the peptide bond in primary structure? Whats released
dehydration
H2O
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?
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.
why can polypeptides form tightly packed globular structures?
b/c the peptide bond is uncharged.
R groups across Peptide bonds nearly always prefer what configuration? and the exception is?
Trans, due to steric clashes.
X-Pro linkages can be both, b/c both are sterically hindered.
Where does rotation about a bond in the aa backbone occur?
The other 2 bonds of the amino Acid, the N-alpha Carbon, Phi bond
and Carbonyl C-alpha C, Psi bond.
Ramachandran diagram tells us what?
Which of all the combinations of Torsion angles from Psi and Phi bonds are possible (ie sterics wont interfere)
What does proline do to Alpha helices? and why?
Disrupts there configuration due to the lack of the H on the N terminus, b/c of the ring causing deprotonation.
Beta strands are unlike an alpha helix in that they are? how many strands make up a sheet?
fully extended and therefore flattened and not compact.
2 or more strands for a sheet
Essentially, all Alpha helices found in Proteins are ________ handed?
Right
Hemeglobin is mostly what secondary structure? why?
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
H bonding in a helix compared to a sheet is similar or different? how so?
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.
Why are antibodies sticky and what happens in Alzheimers?
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.
how many AA residues make up a helix and strand respectively?
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.
the strands of sheets can run in different directions? what are these to formations called and whats different about there bonding?
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.
Polypeptide backbone is formed in what Direction? and what is repeating atom sequence of backbone?
N to C with N being the beginning and C the tail.
NCC NCC NCC NCC etc.
on Beta Strand, what is the distance between consecutive R groups on one side of a sheet?
7A for every other, b/c its 3.5A between aa but the R groups alternate sides of the sheet.
What 2 Fibrous proteins provide structural support for the cells and tissues?
Collagen and alpha Keratin.
What does keratin consist of to form its general structure?
whats unique about keratins AA sequence?
where is it found in the body?
- 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
Whats special about keratins sequence that helps it to for its tertiary structure
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.
Keratin Heptad has how many residues per turn? and why
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.
Whats the most abundant protein in mammels?
what is this protein a component in?
Collagen
the main fibrous component of skin, bone, tendon, cartilage, and teeth
what is collagens structure? in general and what residues make it what it is?
THREE helical polypeptide chains. With glycine appearing every third residue in the sequence, along with Proline, and Hydroxyproline.
Is Collagens internal helical bonding similar to that of other alpha helices?
What about the bonding between the helices, is it like Keratin?
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.
Why does Collagen have this repeating every 3 GLY residue structure?
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.
