Term
| Drugs having effect on proteins |
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Definition
1.Gleevec - CML Cancer Drug, GF Inhibitor for WBC
2.Herceptin-HER2 GF inhibitor
3.Celebrex-COX Inhibitor Arthritis
4.Cialis-Guanylate Cyclase and cGMP
5.Prempro-Estrogen mimic |
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Term
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Definition
1.Humulin-rDNA insulin from e. coli
2.Herceptin
3.Epogen-Stimulate RBC production
4.BeneFIX-Coagulation Factor IX recombinant
5.Neumega-IL-11 platelet production |
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Term
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Definition
1.20,488 genes for diff. proteins
2. |
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Term
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Definition
| Deermination of structure, function, interaction, expression, location, modifications, timing of proteins to define tissue, organ, organ system, organism. |
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Term
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Definition
Majority of Proteins
1.Enzymes
2.Igs
3.Receptors
4.Transcription Factors
5. Channels |
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Term
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Definition
Provide Structure and contribute majority of bulk of an organism
1. Skeletal
2.Transient structures (Fibrinogen in blod clots)
3.Cytoskeleton
4.ECM
5.Contractile structures in muscle |
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Term
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Definition
C-H bond 10^-10m
Molecules 1-10nm
Cell 1um or 1,000nm
Time in milli and micro seconds |
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Term
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Definition
1.Primary: covalently bonded amino acid sequence
2.Secondary: H-bonded repetitive structures
3.Tertiary: Spatial Interactions including primary and secondary
4.Quarternary: Multiple polypeptide sub-units (homo and hetero) |
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Term
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Definition
| 20 used in human proteins, in "L" form, all same basic structure except proline (cyclic), encoded by three letter DNA code (3bp = 1aa). |
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Term
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Definition
1.Basic-Argenine, Lysine, Histidine
2.Acidic-Glutamate, Aspartate
3.Sulfur-Cysteine(S-S bonding), Methionine (start codon)
4.Phosphorylatable-Tyrosine, Serine, and Threonine |
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Term
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Definition
Most are in trans formation
Phi N & alpha-C (-60degrees in helices)
Psi alpha-C & CO (-60degrees in helices)
Condensation to form, Hydrolysis to break |
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Term
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Definition
1.Edmann degradation Phenylthioisocyanate label N-term, acid, chroma., repeat
2.Sanger Method-DNA sequencing |
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Term
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Definition
1.Helices: alpha hellix most common
2.Beta Pleated Sheets: parallel and anti-parallel
3.Beta Turns |
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Term
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Definition
Phi and Psi both at -60 degrees
H-bonds between peptide backbone CO and NH 4aa apart.
right handed helices
Alpha coiled coil such as keratin
Used to span across cell membrane |
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Term
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Definition
parallel
anti-parallel
mixed
H-bonding of peptide backbone |
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Term
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Definition
1.Surface of proteins
2.site for glycosylation
3.Immuno recognition
4.Predictable |
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Term
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Definition
Stabilized by weak bonding
R groups are major players
Not predictable
dictated by primary sequence |
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Term
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Definition
Stabilized by weak bonding
R groups are major players
Not predictable
dictated by primary sequence |
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Term
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Definition
1.Globular
2.Driven by burying hydrophobic regions
3.Surface residues are polar
4.Charge pairs only when no water
5.Pi Stacks: aromatic R groups stabilize
6.Key positions are very specific in R group
7.Native Conformation: lowest energy form |
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Term
Protein Folding (cont.)
and Diseases |
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Definition
Chaperones and Chaperonins help keep proteins from mis-folding and sticking in wrong ways and sites.
1.Creutzfeldt-Jakob (madcow, scrapie)
2.Alzheimers |
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Term
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Definition
| Misfolded protein is template for ther proteins to misfold and accumulate into amyloid plaques. These are infectious. |
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Term
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Definition
1.Folds on own
2.Secondary structure connected by loops
3.Own Hydrophobic core
4.Ind. funtional and structural property
Examples are proteins that have binding domains, kinase domains, etc. |
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Term
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Definition
Units within domains
Ex:1)GXGXPhiG: Binds PO3 of ATP
2)DFG: coordinates Mg binding to PO3 of ATP |
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Term
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Definition
Disulfide Linkages: Cys-Cys sulfur groups bind proteins to themsleves, to other proteins, and more
Immunoglobulins and Insulin are good examples |
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Term
| Protein Structure Determination |
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Definition
1.X-Ray Crystallography: crystallize proteins, shoot x-rays, measure diffraction pattern, mathematically workout structure
2.NMR: Protein in solution, complex spectral data, only up to 900aa |
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Term
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Definition
1.Size
2.Shape
3.Charge
4.Location |
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Term
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Definition
50,000-70,000 Dalton
avg. amino acid is 100 Da
avg. protein is 500 to 700 aa's
Super large ex. dystrophin is 3685. Doesn't get translated before cell cycles often. |
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Term
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Definition
1.Globular - dominant type
(e.g.enzymes)
2.Structural - elongated (e.g. collagen, elastin, keratin) |
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Term
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Definition
1. 10 isoforms
2. 3 polypeptides (2 alpha and 1 beta chains) twisted in rt. handed triple helix
3. those fibers form fibrils
4. Glycine is major constituite
5.Starts folding in ER at COOH end
6. Gly-X(proline)-Y(hydroxyproline) |
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Term
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Definition
1.Osteogenesis Imperfecta: Gly is replaced destabilizeng collagen. If close to COOH the problem is worse. Dominantly inherited (25% spontaneous)
2. Scurvy |
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Term
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Definition
1.Type I (N-terminus EC) Type II (C-terminus EC)
2.Multiple passes
3.Glyosylattion and disulfide bonds EC
4.Thiol, Phosphorylation IC |
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Term
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Definition
Extrinsic to membrane
Lipophilic anchors |
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Term
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Definition
1.Charged R groups: Glu, Asp, His, Arg,Lys
2.N and C termini
3.Modifications (PO3-)
4.Metal Ions |
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Term
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Definition
[H][A]/[HA]
equilibrium constant
pKa is pH at which R group is charged |
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Term
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Definition
Isoelectric Point - Point at which protein has no net charge.
Used in Isoelectric focusing |
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Term
| Protein Localization and Targeting Sequences |
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Definition
1.Nucleus: KKXK or (K/R)2-x10-12-(K/R)
2.Peroxisome: SKL-COO terminus
3.Mitochndria: N-terminal amphipathic helix
4.ER: KDEL-COO terminus |
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Term
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Definition
1.N-linked: sugar on N of Asp
2.O-linked: sugar on OH of Ser or Thr |
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Term
| Mitochondrial Localization of Proteins |
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Definition
Two Membranes to cross.
Tom on outer and Tim on inner.
Folded inside Mitos.
No Sugars, no S-S, free N-terminus when targeting sequence is clipped (unlike cytosolic proteins) |
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Term
| Protein harvesting and characterization |
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Definition
1.Crude (ppt and dialysis)
2.Ion-exchange (charge)
3.Gel Filtration (size)
4.Absorption (hydrophobicity)
5.Affinity (Interaction with other molecules like Ig, Metals
6.Preparative electrophoresis (SDS-PAGE) |
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Term
| Protein Sequence Comparison |
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Definition
1.Same function across species, similar sequences
2.Tertiary structure may be more conserved than primary sequence
3.Convergent evolution |
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Term
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Definition
Orthologues: Same protein in different species
Paralogues: Gene duplication within same organism |
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Term
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Definition
| Hb in Sickle Cell is a point mutation, E is changed to V |
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Term
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Definition
Allo-form of protein begat by alleles of same gene
Iso-proteins from different genes, but catalyze same reaction (kinetically different often)
Isozyme example: LDH is tetramer (homo and hetero) in muscle(M)and heart(H) are isozymes. H has higher affinity for S than M. H inhibited by pyruvate, not M. M functions in anaerobic enviro., H in aerobic. LDH profile changes over time. |
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Term
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Definition
Creatine Kinase-2: activity peaks at 24hr after MI
LDH peaks at 36-40hr post MI |
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