Protein structure 1 Flashcards
What types of hetero groups are there
- Metals
- Non-metals (sulphur, selenium)
- Organic molecules
What are the different types of binding of a hetero group
- Permanent: metals, organic prosthetic groups
2. Transient: substrates, coenzymes, regulators
What hetero groups are used in pyruvate dehydrogenase and what are their function
1 Has 5 cofactors:
- TPP
- Lipoic acid
- CoA
- NAD
- FAD
- The cofactors facilitate the oxidative decarboxylation of pyruvate
- The cofactors have diverse chemical structures
What do double bonds mean
- Double bonds allow very little freedom of rotation
2. The resulting configurations may be either cis or trans
What is a chiral centre
- Chiral centers – asymmetric carbons, exist as two stereo-isomers, which are mirror images (enantiomers)
What are dia-steroisomers and how are they labelled
- dia-stereoisomers - stereoisomers with more than one chiral center; they are not mirror images
- Absolute configurations: R / S
- Relative configurations: D / L
- Nearly all amino acids in proteins possess the L configuration
What are amino acids often grouped by
- Amino acids are commonly grouped by side-chain polarity:
- Polar side-chains:
- Due to difference in electronegativity (O,N)
- Due to difference in electron density (S)
- Nonpolar side-chains –
- contain only C-H, C-C, and C-S-C bonds
Why is polarity important
- Underlies non-covalent interactions:
- Drives protein folding and determines amino acid distribution (protein-protein, protein-water interactions)
- Drives protein-ligand binding
Give some examples of certain chemical derivatives of amino acids
- Hydroxyproline- post-translational
- gamma-carboxy-glutamate - post-translational
- seleno-cysteine- incorporated
- Pyrrolysine- incorporated
What are roles of some amino acid derivatives
- Some non-protein amino acid derivates are biologically active
- NMDA
- Melatonin
- Serotonin
Describe the peptide bond
- Resonance makes the peptide bond:
2. Partially double –> planar yet not completely rigid
How does the primary structure hold biological information
- Biologically important residues (ligand binding, catalysis) tend to be evolutionary conserved
- Such residues can be found by aligning sequences of the same protein from different organisms
- Membrane-bound proteins contain hydrophobic sequences with lengths matching the membrane width
How does the protein fold
- Small protein can fold independently (Anfinsen’s experiment with ribonuclease A)
- Large proteins fold with the assistance of molecular chaperons
What are the two configurations the peptide bond is limited to
- The rotation of the Cα-N and Cα-C bonds is limited only by steric clashes
- The ‘allowed’ values of phi and psi angles correspond to two main conformations
What are two exceptions to the spiral and extended conformations being highly popular in proteins
- The two exceptions are Pro and Gly
What are different graphic representations of proteins that reveal different properties
- Wireframe (bonds connectivity)
- Space-fill (general shape, size) - Space-fill, colored by evolutionary conservation (biologically important regions)
- Ribbon (topology, secondary structures)
- Surface (potential binding sites) - Surface, colored by electrostatic potential (complementarity to ligands)
- Integrated (multiple properties)
Describe properties of the right-handed alpha-helix
- ~30% of residues in globular proteins
- Radius: 2.3 Å
- 5-40 residues (10 average)
- 3.6 residues per turn (5.4 Å)
- phi = -57o, psi = -47o
- 1.5 Å rise per residue (compact)
Describe Stabilization of right handed alpha helix
- Mainly nonpolar & vdW interactions
2. Hydrogen bonds – much weaker (exist also in the unfolded state)
Describe Amphipathic helices
- Polar/nonpolar residues face opposite directions
- Same-type residues appear every 3 or 4 positions
- Tend to appear on the surface of proteins
What are other types of helix
- The 310 helix
- The π helix
- The PPII helix
Describe the 310 helix
- Tighter than α-helix –> unfavorable packing & H-bond pattern
- Rare (4%), usually found as a single turn at the beginning/end of alpha helices
- Roles: connecting secondary elements, fixing distortions formed within α-helices (e.g. by Pro)
Describe the pi-helix
- Wider and less tight than α-helix –> sub-optimal vdW interactions, unfavorable H-bond pattern
- Extremely rare (~0.02% of protein residues)
- Usually found at the beginning/end of alpha helices
- Roles: unclear
Describe the PPII helix
- Left-handed, created by proline-rich sequences (but appears also in other sequences)
- Long and thin -> no backbone H-bonds
- In structural proteins (e.g. collagen) – creates the tightly packed triple helix
- In globular proteins – tends to be amphipathic, on surface, functionally important (e.g. bound by SH3 domain)
- SH3 domain – appears in signaling proteins, recognizes PPII helices in binding partners to relay the signal
Describe the beta (extended) conformation
- ~20% of residues in globular proteins
- Up to ~10 residues per strand
- ~3 Å rise per residue (extended)
- The sheet has a ~30º right twist
Why are helices and sheets so common?
- 90% of polar groups in proteins are hydrogen-bonded
2. Helices and sheets pair polar groups most efficiently
What are reverse turns and where do they occur
- 2nd position - usually cis-Pro (creates a kink )
- 4th position – Gly (accommodates the kink )
- 3rd and 4th positions – not conserved (yet, often Asn/Asp)
- i –> i+3 hydrogen bond
What are loops
- Connect secondary structure elements
- Usually hydrophilic (polar residues, unsatisfied backbone H-bonds)
- On the surface
- Often create binding/active sites of receptors and enzymes
- Secondary elements are more ordered than loops
