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The Amino AcidsProtein Structure
BIOCHEM 301 SUMMER 2014Lectures 4 and 5
Wednesday, September 3, 2014Monday, September 8, 2014
Amino Acids
(normal form)
Name Three-Letter Code
One-Letter Code
Alanine Ala AArginine Arg RAspartate Asp DAsparagine Asn NCysteine Cys CGlycine Gly GGlutamate Glu EGlutamine Gln QHistidine His HIsoleucine Ile ILeucine Leu LLysine Lys KMethionine Met MPhenylalanine Phe FProline Pro PSerine Ser SThreonine Thr TTryptophan Trp WTyrosine Tyr YValine Val V
FYI: Essential Amino Acids• Essential (humans do not make):
– Arg, His, Ile, Leu, Lys, Met, Phe, Thr, Trp, Val
• Non-essential (humans make):– Ala, Asn, Asp, Cys, glu, Gln, Gly, Pro,
Ser, Tyr
Other Amino Acids• 4-hydroxproline found in collagen• ornithine and citrulline are N
metabolism intermediates
Sidechain pKa ValuesAmino Acid Sidechain pKa
Asp 3.6Glu 4.3His 6Cys 8Tyr 10Lys 10.5Arg 12.5
Expected Protonation State, pH 7?
Amino Acid Sidechain pKa
Protonated?
Asp 3.6 NoGlu 4.3 NoHis 6 NoCys 8 YesTyr 10 YesLys 10.5 YesArg 12.5 Yes
Sidechain pKa Values: Why?• Glu, Asp• Lys, Arg• Cys, Tyr• His• and what about Ser and Thr?
Perturbation of pKa Values• What factors could raise a sidechain
pKa from its normal value?• What factors could lower a sidechain
pKa from its normal value?
The Peptide Bond
Peptides
N- and C-Termini• First “residue” = N-terminus
– Has an amino group with pKa = 9• Last “residue” = C-terminus
– Has a carboxyl group with pKa = 2• Amino and carboxyl groups of all
other residues participate in peptide bonds and cannot protonate/deprotonate
Sequences and Residue Numbers
• Sequences are written using one-letter codes– Ex: MEGTNPEFDLVW...
• Residues are numbered from 1 at N-terminus, and identified using the amino acid type– Ex: L10
• Engineered mutations add one more letter– Ex: L10A means L10 is mutated to Ala
Peptides
The peptide bond has a partial double bond character.This helps to enforce the trans configuration.
Peptides
Catalyzed by Proline isomerase enzymes
Jane Richardson. “The Anatomy and Taxonomy of Protein Structure.” Advances in Protein Chemistry, 34 (1981).
Disulfides
Bovine insulin
The Alpha Helix
The Beta Sheet
An Antiparallel Beta Sheet
Cu/Zn superoxide dismutase
A Parallel Beta Sheet
Flavodoxin
Everything Else• Loops or turns connect secondary
structural elements
Loops and Beta Sheets
Loops and Beta Sheets
Turns
The Ramachandran Plot(no Gly)(no Pro)
The Ramachandran Plot(Gly only)
Deriving the Ramachandran Plot
Crosshatchedregions are possible
The boundariesshow whichsteric clash makesa conformationimpossible
Motifs
Pyruvate kinase
Motifs
Helix-turn-helix motif binds DNA
Ways to Show Structures
Myoglobin
Heme in redHydrophobics in blue
Surface vs. Ribbon Diagrams
All-α, Mixed α/β, All-β
(a)Cytochrome b562(b)NAD-binding domain of lactic dehydrogease(c) Immunoglobulin light chain, variable region
Antiparallel Up/Down Alpha Helix Bundles
“Greek Key” Organization
Greek key =decorative elementin Greek andRoman mosaics
Antiparallel “Greek Key” Alpha Helix Bundles
Greek key =decorative elementin Greek andRoman mosaics
Parallel Alpha/Beta Singly Wound Barrels
Parallel Alpha/Beta Doubly Wound Sheets
Parallel Alpha/BetaDoubly Wound Sheets
Antiparallel Beta Greek Key Barrels
Antiparallel Beta “Jellyrolls”
Antiparallel Beta “Open-Face Sandwiches”
Dimers
Multimers
One Chain vs. Many Chains
Src protein: Four domains, one chain
Multimers• Example: hemoglobin
– Two “alpha” and two “beta” subunits– Symmetric– Four heme groups
GroEL/GroES
Protein Assemblies
Protein Assemblies
Protein Assemblies
Protein Assemblies
Virus Capsids
Tomato BushyStunt Virus
Virus Capsids
(a)Tomato bushy stunt virus (c) SV40(b)Poliovirus (d) Satellite tobacco necrosis virus
Proteins and Membranes
(1)Single alpha helix(2)Multiple alpha helices in a bundle(3)Beta barrel(4)Helix in the membrane horizontally(5)Anchored to a lipid(6)Anchored by sugars(7)Anchored by other membrane proteins(8)Anchored by other membrane proteins
Proteins and Membranes• Transmembrane region has exposed
hydrophobics
Alpha Helix Bundles
D Deng et al. Nature 000, 1-5 (2014) doi:10.1038/nature13306
Overall structure of the human glucose transporter GLUT1.
Beta Barrels