The Protein Building Blocks Proteins Are Polypeptide Chains
The Protein Building Blocks
Proteins Are Polypeptide Chains Peptide bond H H N Ca N C Ca O R n+1 O Rn C
The Basic Block: Amino Acid Sidechain R H + N 8. 9 < p. Ka < 10. 8 Ca O 1. 7 < p. Ka <2. 6 C H H H Amino group O Carboxyl group “zwitterion” Convention for atom name: a: A b: B g: G d: D e: E z: Z h: H
The 20 amino acids 1 -letter 3 -letter Amino acid 1 -letter 3 -letter Amino Acid A Alanine M Methionin C Cysteine N Asn Asparagine D Aspartic Acid P Proline E Glutamic Acid Q Gln Glutamine F Phenylalanine R Arginine G Glycine S Serine H Histidine T Threonin I Ile Isoleucine V Valine K Lysine W Trp Tryptophan L Leucine Y Tyrosine
NCBI_Vertebrates
Uni. Prot_Sprot_Human
Uni. Prot_Sprot_Archaea
Uni. Prot_Sprot_Mitochondrion
P 2_eucaryotic P 2_mitochondrion
Small Amino acids: Glycine H CA Highly flexible C
Hydrophobic Amino acids (1) CH 3 CG 2 CG 1 CH 3 CH CB CB CA C C CA Ala Val
Hydrophobic Amino acids (2) CD 2 CD 1 CH 3 CD CH CG CG 1 CH 3 CG 2 CA Leu CH 3 CH CH 2 CB C CA Ile C
Hydrophobic Amino acids (3) CG H C CE 1 CB CZ CD 1 CD CE 2 N CA CH 2 N Pro CG CH CH C CD 2 CB CH 2 CA C C Phe
Hydrophobic Amino acids (4) CE SD CG CB CZ 2 CH 3 S Met CE 3 CH 2 CZ 3 CD 2 CD 1 C CA NE 1 CE 2 CH CG CB H C HC C C H H N CH C CH 2 C CA Trp
Polar Amino acids (1) OG 1 CB OH OG Ser OH CB CH 3 CH CH 2 C CA CG 2 C CA Thr
Polar Amino acids (2) OH OH CE 2 CD 2 CZ CE 1 CG CB CD 1 C CH CH C CH 2 CA C
Polar Amino acids (3) OE 1 OD 1 O ND 2 CB CG NH 2 C O CD CB Asn C C CH 2 CG CH 2 CA NE 2 NH 2 C CA Gln
Polar Amino acids: Cysteine SG CB S CH 2 p. Ka sidechain: 8. 3 C CA SG 1 Can form disulphide bridges in proteins CB 2 CB 1 CA 1 SG 2 CA 2
Polar Amino acids: Histidine NE 2 CD 2 CB CE 1 ND 1 CG N CH CH N C H CH 2 CA C p. Ka sidechain: 6. 04
Different ionic states of the Histidine sidechain H + N CH CH N H C H N CH 2 CH CH N CH C CH 2 C CH N CH 2 CH + CH N C CH 2 C C H H
Charged Amino acids (1) OD 1 O- O CG OD 2 C CB OE 1 OE 2 CG CD CB CH 2 O O C CH 2 C CA CA p. Ka sidechain: 3. 9 Asp C p. Ka sidechain: 4. 25 Glu -
Charged Amino acids (2) NH 2+ NH 2 NZ NH 3+ NH 1 NH 2 CE CD CH 2 CG CZ CZ NE CD NE CG CH 2 CB CH 2 CA p. Ka sidechain: 9. 2 Lys C CB CH 2 CA C p. Ka sidechain: 12. 5 Arg
Unusual Amino Acids: the case of Cyclosporin (Butylmethylthreonine) (amino-butyric) (sarcosine) CH 3
Degrees of Freedom in Proteins Bond length 1 Dihedral angle 2 3 1 2 Bond angle + 4
Protein Structure: Variables Backbone: 3 angles per residue : j, f and w Sidechain: 1 to 7 angles, c; each c has 3 favored values: 60 o, -60 o, 180 o.
The Peptide Bond Peptide bond H H N Ca N O Rn C Ca O R n+1 C The peptide bond is planar H H Ca N C Ca O Conformation “Trans” O N C Ca Conformation “Cis” Ca
RAMACHANDRAN PLOTS y y f All residues, but glycine and proline f Glycine Acta Cryst. (2002). D 58, 768 -776
Amino Acid Chirality R R CA CA H CO N L-form H N CO D-form (CORN rule) Amino acids in proteins have all the L-form Threonine and Isoleucine have a second optical center which is also identical in all natural amino acids.
Sidechain Conformation -Each torsion angle has 3 preferred conformations : g+ (-60), g- (+60), t (180) -c 2 for aromatic sidechains have two preferred conformations: +90, -90 - Not all combinations of c angles are possible: there a few preferred conformations, called rotamers -Many rotamer libraries are available on the web (see for example: http: //dunbrack. fccc. edu/bbdepdownload. php )
Summary • All proteins are polymers built up from 20 amino acids. • Each amino acid shares a common mainchain; the remaining atoms form sidechains, that can be hydrophobic, polar or charged. • The conformation of the mainchain is defined by two dihedral angles, f and y. Only certain combinations of (f, y) are allowed. • Certain sidechain conformations are energetically more favorable: rotamers.
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