Term
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Definition
| the alpha-helices are flanked by Asn or Gln whose side cahins can fold ack and form H-bonds with a helix terminal residue |
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Term
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Definition
| a distortion that occurs at the end of the B-sheets if an extra residue is NOT H-bonded to a neighboring strand |
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Term
| What are turns and loops? |
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Definition
| often appear in protein structures between regular 2nd structures to cause change in direction of peptide chain |
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Term
| What are Reverse Turns or B-bends? |
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Definition
| often connect successive strands of B-sheets, always appear at SURFACE of proteins |
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Term
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Definition
| appear at surfaces, 6-16 residues, usually bigger |
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Term
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Definition
| disordered state of totally unfolded (denatured) proteins that have lost their native (bio. functional) conformation, may rapidly fluctuate in solution, NOT really always coiled nor really random |
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Term
| What techniques are used for tertiary structures: |
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Definition
1) X-ray crystallography
2) X-ray diffration
3) NMR
4) Neutron Diffration |
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Term
| What must you have for X-ray diffraction? |
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Definition
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Term
| How do you get higher resolution in diffraction pattern? |
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Definition
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Term
| How do you get more data in electron density maps? |
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Definition
| more time(50% more data at ~1.1 A is very good) |
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Term
| How much water is in a typical protein? |
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Definition
| 40-60% (so protein is essentially in solution) |
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Term
| How do protein crystals compare to other small molecules as seen in X-ray structures of proteins? |
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Definition
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Term
| What are active in cystalline forms of proteins? |
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Definition
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Term
| What are "habitats" in X-ray structures of proteins? |
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Definition
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Term
| In X-ray structures of proteins, different crystal forms yield what? |
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Definition
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Term
| Why are NRM structures are possible? |
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Definition
| the development of multidiminsional techs. |
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Term
| NMR structures determined what? |
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Definition
| distance constraints (NOT angles) between protons < 5 A apart by through space Nuclear overhauser effect spec. (NOISY) or through bonds in collelation spec. (COSY) |
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Term
| NMR structures generates data that does what? |
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Definition
| a set of structures (in solution) that are self consistent |
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Term
| In NMR structures, moving of family of structure is due to what? |
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Definition
| thermal movements of salt |
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Term
| Where do nonpolar side chains tend to be? |
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Definition
| in the interior of structure, away from water |
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Term
| Charged polar groups in proteins tend to be where? |
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Definition
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Term
| Uncharged polar side chains in proteins tend to be where? |
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Definition
| on surface or interior (if interior, then H-bonded, tend to be compact and tightly packed with no water) |
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Term
| What do B-Barrels arise from? |
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Definition
| anitparallel B-pleated sheets (tend to rotate in space) |
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Term
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Definition
| structually independent regions of proteins that may have different funtions, tend to consist of 100-200 amino acids that act like globular proteins with average radii ~25 A |
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Term
| How many domains does Glyceraldehyde 3-phosphate dehydrogenase have? |
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Definition
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Term
| What are protein families? |
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Definition
| groupings of many thousands of known proteins structures that comprise an even greater number of separate domains, grouped by examining the overall paths followed by their polypeptide chains, implies that essential structures and functions are conserved |
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Term
| How many protein domain families are there? |
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Definition
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Term
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Definition
| porteins with more than 1 subunit, may have idential or different subunits, some enzymes may have >1 active site where catalysis occurs |
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Term
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Definition
| idenitical subunits (can have 1 type of polypeptides or several different ones) |
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Term
| What are similar to interior regions of globular proteins and how? |
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Definition
| contact regions, tightly packed subunits are held together by hydrophobic interactions, H-bonds and sometimes disulfide bonds |
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Term
| Hemoglobin, oligomer- 2alpha and 2 beta subuits, or 2alpha-beta protomers are subunits that are what? |
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Definition
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Term
| What is rotational symmetry? |
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Definition
| subunits that have symmetric arrangements in space, can go back to original symmetry, rotate 180 degrees is the same C2 symmetry |
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Term
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Definition
| only marginally, can be denatured by ~0.4 kJ mol-1residue-1 (typically H bond is ~20 kJmol-1) |
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Term
| What contribute to protein stability? |
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Definition
1)hydrophobicity of an interior residue
2)steric compatability
3)side chain volume |
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Term
| What works best for hydropathy plot? |
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Definition
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Term
| What are electrostatic interactions? |
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Definition
| ion pairs or salt bridges, ~75% at surfaces of prooteins, side chains must loose entropy (to be in close proximity to) and water of solution, can veyr rarely occur in interior of protein where there is NO water |
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Term
| Why are H-bonds important for protein stability? |
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Definition
| highly anisotropic (directional), therefore most important in terms of providing specificity, NOT stability, but do provide some stability |
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Term
| What role do disulfide bonds play in protein stability? |
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Definition
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Term
| Do metal complexes play a role in protein stability? |
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Definition
| yes, Van der Waals = isotropic = result in folding) |
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Term
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Definition
| d(10), can form coordination complexes with O,N, or S ligands, Zinc-finger canNOT modify Zn |
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Term
| What is protein dynamics? |
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Definition
| *protein structures flucuate ~2 A (even more at surface) on the femtosecond timescale |
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Term
| How does heat cause proteins to unfold? |
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Definition
| cooperatively (unfolding of 1 part causes next part to unfold even easier or faster), most proteins denature well below 100 degrees C |
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Term
| What are Cahoptropic or Lyotropic Agents? |
|
Definition
| 5-10 M solutiosn that make nonpolar solutes more soluble in water by disrupting the bulk water structure |
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Term
| Why is urea water soluble? |
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Definition
| it disrupts water structure |
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Term
| What did Christian Anfinsen do? |
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Definition
| renaturation of RNAse, no enzymatic activity, remove urea vy dialysis (becomes active again), disulfide bonds are critical for protein structure |
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Term
| What is the Levinthal Paradox? |
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Definition
-each residue in protein has 2 torsion angles so there are 2n such angles for a protein with n residues,
-if each residue has 3 stable c.f.s, then 3^(2n) or ~10^(n) are possible (ignoring the side chains),
-if n=100 and can sample c.f. in 10^(-13)s, time required to fold t = (10^(100)c.f.s)(10^-13)c.f.^7) = 10^(87)s, universe is ~6X10^(17)s old |
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Term
|
Definition
| by specfic pathways of intermediates, experiemnts show that there is hiearchy of intermediates, 1st(ms) get 2nd structural elements, then(ms) hydrophobic collapse to molten globule state, then(s) 3rd structure forms, floowed by domains and oligomers |
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Term
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Definition
| Folding Funnels (2-D), might be different path of folding of the same peptide to native state (different kinetic path) |
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Term
| What is protein disulfide isomerase? |
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Definition
| catalyzes disulfide exchange, 1st part is made before 2nd part, steps where other porteins catalyze protein rxns, reduced protein may be in presence of mercapthoil |
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Term
| What are molecular chaperones? |
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Definition
| porteins that bind (invitro) unfolded and partially folded polypeptides to prevent aggregation and precipitation, originally called heat chock proteins because abundant under high temp. conditions |
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Term
| What are the classes of molecular chaperones? |
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Definition
| Hsp70 family (monomeric, 70 kD, along iwth cochaperone Hsp40 bind nascunt polypeptides while bound to ribosome), chaperoins (oligomers), and Hsp90 family (folding signal transfuction proteins) |
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Term
| What are E.coli chaperonins? |
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Definition
| GroEL - 14 idential subunits, opening center, GroES: 7 subunits |
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Term
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Definition
| ave. of 24 folding cycles required to attain folded state, iterative process, interior, more hydrophobic region, ATP binding sites, ATP hydrolysis, on the other side can bind imporperly folded protein, resulting protein has more Van der Waals interactions |
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Term
| Empirical methods- homology modling of protein structure prediction? |
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Definition
| aligns target protein sequence with a homologous protein structual genomi approach, reslies on determing structures of all domain, threading, 2nd structure pridictions by Chou-Fasman rules or similar routines work well for 2nd structure, but less well in proteins |
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Term
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Definition
| part of empirical methods- homology moldeing of protein structure prediction, tries to align target sequence on backbone of known structure |
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Term
| What is the Abinito methods for protein structure prodictions? |
|
Definition
| very complex calculations |
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Term
|
Definition
| David Baker, can calculate ~40 amino acids, can be ~80-85% correct |
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Term
|
Definition
| Zinc finger protein Zif268 and synthetic 28 residue FSD-1 |
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Term
| What is Alzheimer's disease? |
|
Definition
|
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Term
|
Definition
| transmissible spongioform Encephalopathies (TSEs), include scrapie, bonvine sp.en. (BSE, Mad Cow), Karu, Creulzfeldt-Jacob disease (CJD), caused by poteinaceous infectios particle (Prion) that has NO nucleic acid |
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Term
|
Definition
| scrapie prion has 208 mostly hydrophobic residues that causes formation of insoluble rods, normal PrP is induced to form abnoraml PrP(SC) by presence of PrP(SC), goes from alpha-helicl c.f. to B-sheet conformation that aggregates |
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Term
| What are encephalopathies? |
|
Definition
| causews plack, infecteous, PrP: alpha to B-sheets |
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Term
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Definition
|
|
Term
| What does a model for PrP(SC) look like? |
|
Definition
| anitparallel B-sheet, polymers of abnormal P |
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Term
| What forms of proteins infect the brain? |
|
Definition
|
|
Term
| In electron micrographs of a cluster of partially proteolyzed prion rods, the colloidal gold beads that are soupled to anti-PrP antibodies adhere to what? |
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Definition
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