Bioinformatics

Biological Basics

1. Amino acids I 2. Peptide bond I 3. Proteins I 4. DNA I 5. Miscellaneous

3. Proteins

• macromolecules / polymers
• 'workhorses of the cell'
• made up of various L-amino acids connected by peptide bonds
• linear chains (unbranched)
  • protein molecule that consists of a single polypeptide chain is said to be monomeric
  • proteins made up of more than one polypeptide chain are called oligomeric
• interact with other proteins, nucleic acids, small molecules, ions, etc.

Protein Structure

Tertiary structure

• 3D arrangement of the amino acid side chains with each other and the main chain
• polypeptide chains bend and fold in order to assume a more compact, specific three dimensional shape
• unique, reproducible 3D structure
  • for instance, many proteins adopt a globular shape because that gives the lowest surface-to-volume ratio
• overall 3-D arrangement of the protein; considers how the various parts of secondary structure are oriented
• stabilized by the complete set of interactions including the flexibility and rotation of the protein backbone and steric hindrance
  • hydrogen bonding, salt bridges between opposite charges (electrostatic interactions), hydrophobic interactions and disulfide bonds

classes in protein architecture

α-proteins

proteins composed mainly of α-helices (often symmetrical around a central hydrophobic core)   all α proteins PDB code 1enh 1bcf 1ao6 Fold DNA/RNA-binding 3-helical bundle Ferritin-like Serum albumin-like Fold description core: 3-helices; bundle, closed or partly opened, right-handed twist; up-and down core: 4 helices; bundle, closed, left-handed twist; 1 crossover connection multihelical; one domain consists of two similar disulfide-linked subdomains Superfamily Homeodomain-like Ferritin-like Serum albumin-like Family Homeodomain Ferritin Serum albumin-like Protein Engrailed Homeodomain Bacterioferritin (cytochrome b1) Serum albumin Species Drosophila melanogaster Escherichia coli Human (Homo sapiens) All α proteins (SCOP)

ß-proteins

proteins composed mainly of ß-sheets   all ß proteins PDB code 1hoe 1jpc 1cd8 Fold α-Amylase inhibitor tendamistat ß-Prism II Immunoglobulin-like ß-sandwich Fold description sandwich; 6 strands in 2 sheets consists of 3 4-stranded sheets; strands are perpendicular to the 3-fold axis duplication: consists of two domains of this fold sandwich; 7 strands in 2 sheets; greek-key some members of the fold have additional strands Superfamily α-Amylase inhibitor tendamistat α-D-mannose-specific plant lectins Immunoglobulin Family α-Amylase inhibitor tendamistat α-D-mannose-specific plant lectins V set domains (antibody variable domain-like) Protein α-Amylase inhibitor tendamistat Lectin (agglutinin) CD8 Species Streptomyces tendae Snowdrop (Galanthus nivalis) Human (Homo sapiens) All ß proteins (SCOP)

α/ß-proteins

proteins that are folded with alternating α-helices and ß-strands   all α/ß proteins mainly parallel ß sheets (ß-α-ß) PDB code 1hti 1oi7 1pfk Fold TIM ß/α-barrel NAD(P)-binding Rossmann-fold domains Phosphofructokinase Fold description contains parallel ß-sheet barrel, closed; n=8, S=8; strand order 12345678 core: 3 layers, α/ß/α; parallel ß-sheet of 6 strands, order 321456 consists of two non-similar domains, 3 layers (α/ß/α) each Domain 1 has mixed sheet of 7 strands, order 3214567; strands 3 & 7 are antiparallel to the rest Domain 2 has parallel sheet of 4 strands, order 2314 Superfamily Triosephosphate isomerase (TIM) NAD(P)-binding Rossmann-fold domains Phosphofructokinase Family Triosephosphate isomerase (TIM) CoA-binding domain Phosphofructokinase Protein Triosephosphate isomerase Succinyl-CoA synthetase, α-chain, N-terminal (CoA-binding) domain ATP-dependent phosphofructokinase Species Human (Homo sapiens) Thermus thermophilus Escherichia coli α and ß proteins (a/b) (SCOP)

α+ß-proteins

proteins that combine α-helices and ß-strands that are largely separated (located in different domains)   all α+ß proteins mainly antiparallel ß sheets (segrated α and ß regions) PDB code 1i8t 1ema 1p27 Fold FAD-linked reductases, C-terminal domain GFP-like Mago nashi protein Fold description α+ß sandwich ß-sheet folds into a barrel (n=11, S=14) around the central helix ß(4)-α-ß(2)-α; 2 layers: α/ß; antiparallel ß-sheet, order: 651234 Superfamily FAD-linked reductases, C-terminal domain GFP-like Mago nashi protein Family UDP-galactopyranose mutases Fluorescent proteins Mago nashi protein Protein UDP-galactopyranose mutases Green fluorescent protein, GFP Mago nashi protein Species Escherichia coli Jellyfish (Aequorea victoria) Human (Homo sapiens) α and ß proteins (a+b) (SCOP)

multi domain proteins (α and ß)

multi-domain proteins; folds consisting of two or more domains belonging to different classes   multi-domain proteins (α and ß) PDB code 1hle 1ab4 1m7s Fold Serpins Type II DNA topoisomerase Heme-dependent catalases Fold description contains a cluster of helices and a ß-sandwich 4 domains: (1) toprim α/ß; (2) "winged helix"-like; (3) α+ß; (4) all-α contains an (8,10) ß-barrel and an all-α domain Superfamily Serpins Type II DNA topoisomerase Heme-dependent catalases Family Serpins Type II DNA topoisomerase Heme-dependent catalases Protein Elastase inhibitor DNA Gyrase A Catalase I Species Horse (Equus caballus) Escherichia coli Pseudomonas syringae Multi-domain proteins (α and ß) (SCOP)

• LIFE - The Science of Biology (7th edition) (by W.K. Purves, D. Sadava, G.H. Orians, H. Craig Heller)
• Protein Structure by Molecular Graphics (University of Cambridge)
• Protein Structure Classification (by O. Lund, Technical University of Denmark)
• Protein Structure: Understanding Protein Conformation (by H. Jakubowski, St. John's University)
• Cozzone, A.J.; Encyclopedia of Life Sciences 2002, 1-10. Proteins: fundamental chemical properties. [PDF]
• Hadley, C.; Jones, D.T.; Structure Fold. Des. 1999, 7(9), 1099-1112. A systematic comparison of protein structure classifications: SCOP, CATH and FSSP. [PubMed]
• Ouzounis, C.A.; Coulson, R.M.; Enright, A.J.; Kunin, V.; Pereira-Leal, J.B.; Nat. Rev. Genet. 2003, 4(7), 508-519. Classification schemes for protein structure and function. [PDF I PubMed]
• Saito, N.; Adv. Biophys. 1989, 25, 95-132. Principles of protein architecture. [PubMed]
• Shakhnovich, B.E.; Max Harvey, J.; J. Mol. Biol. 2004, 337(4), 933-949. Quantifying structure-function uncertainty: a graph theoretical exploration into the origins and limitations of protein annotation. [PubMed]

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