结构生物化学Chapter2 Structure of proteins

☺1838 Berzelius – “Proteins” from the Greek “of 1st rank or importance”
☺Central Dogma: DNA RNA protein (information flow)
☺DNA, RNA information is in the sequence - linear ☺Protein function is in the 3D structure
☺Cofactors are non-amino acid components e.g. metal ions like Zn2+ in carboxypeptidase
☺Coenzymes are organic cofactors e.g. nucleotides in lactate dehydrogenase
1. Primary structure of proteins 2. Secondary structure of proteins 3. Tertiary structure of proteins 4. Quarternary structure of proteins
@ Protein folding pathways and structure prediction
the free COOH group is on the right. E N-terminus: alanine E C-terminus: aspartic acid E Ala-Asp E alanylaspartic acid
Peptides
« Tripeptides
peptide bond peptide bond
Peptides & Proteins
Peptides contain 50 or fewer amino acids and are further classified below.
«Dipeptides contain 2 amino acids. «Tripeptides contain 3 amino acids. «Oligopeptides contain 4~10 amino acids «Polypeptides contain 50 or fewer amino acids. «Proteins contain greater than 50 amino acids. «An amino acid in the peptides or proteins is
Chapter 2 Structure of proteins
Outline
@ Peptides
1. Definition, classification and Nomenclature of peptides 2. Properties of peptides
@ Structure of proteins
① synthesized by a series of enzymes outside the ribosome
② may contain D-aa ③ an example: glutathione
Properties of Peptides
☺Novel acid-base properties -also have pI
« Secondary Structure (2º) : regular repeating structures of the polypeptide chain (i.e. α-helices, β-sheets) ;coiling /folding as a result of hydrogen bonding
☺Biruet reaction (except for dipeptide) ☺Chirality ☺Degradation ☺Biological function
Proteins
☺1830 Mulder – what remained after removal of sugars, fats, salts, etc.
The amino acid sequence of a protein is specified by the gene encoding that protein
DNA: ggc att gtg gaa caa tgc tgt acc agc mRNA: ggc auu gug gaa caa ugc ugu acc agc Protein: Gly-Ile-Val-Glu-Gln-Cys-Cys-Thr-Ser
“Diversity of Proteins”
One or more polypeptide chains ☺ One polypeptide chain - a monomeric protein ☺ More than one - multimeric protein ☺ Homomultimer - one kind of chain ☺ Heteromultimer - two or more different chains ☺ Hemoglobin, for example, is a heterotetramer ☺ It has two alpha chains and two beta chains
Insulin was the first polypeptide to be sequenced (by Frederick Sanger in 1953). The sequencing of insulin demonstrated for the first time that proteins are composed of specific, defined amino acid sequences.
called amino acid residue «Peptide chain and Polypeptide chain
Peptides
« Dipeptides: two amino acids linked by peptide bond (amide
linkage)
peptide bond
O
O
H2N CH C OH + NH2 CH C OH
CH3
CH2CO2H
alanine
aspartic acid
_ H2O
O
O
H2N CH C NH CH C OH
CH3
CH2CO2H
Ala-Asp
Peptides are written so that the free NH2 group is on the left and
1. General principles of protein folding 2. Protein folding pathways 3. Some diseases related to protein misfolding
@ Protein structure prediction @ Proteome and proteomics
The Peptide Bond
☺has partial (40%) double bond character ☺is about 0.133 nm long - shorter than a typical
single bond but longer than a double bond ☺Due to the double bond character, the six atoms
terminus
1o structure =linear amino acid sequence
For the Insulin A chain, the 1o structure is: Gly-Ile-Val-Glu-Gln-Cys-Cys-Thr-Ser-Ile-Cys-Ser-
Leu-Tyr-Gln-Leu-Glu-Asn-Tyr-Cys-Asn
☺Prosthetic groups are tightly attached cofactors e.g. heme in myoglobin
Hierarchy of protein structure
« Primary Structure (1º) : Unique sequence of amino acids: sequence is determined by genetic material
① coded by their own genes ② synthesized in the form of precursor ③ never contain D-aa ④ an example: oxytocin
« Peptides not synthesized on the ribosome
« Tertiary Structure (3º) : 3-D shape due to bonding of Rgroups
« Quaternary Structure (4º) : association of 2 or more polypeptides; Ex HGB ; not all have this level
“Diversity of Proteins”
Proteins - Large and Small ☻Insulin - A chain of 21 residues, B chain of 30
residues -total mol. wt. of 5,733 ☻Glutamine synthetase - 12 subunits of 468 residues
Four levels of protein structure
Primary: amino acid sequence Due to covalent bond
The Sequence of AA in a Protein
«is a unique characteristic of every protein «is encoded by the nucleotide sequence of DNA «is thus a form of genetic information «is read from the amino terminus to the carboxyl
Hierarchy of protein structure
Primary
Primary
- sequence
Tertiary
Secondary
- e.g -helix or -sheet
Tertiary
- 3D shape
Quaternary
Quaternary
- subunit organization (> one polypeptide chain)
each - total mol. wt. of 600,000 ☻Connectin proteins - alpha - MW 2.8 million! ☻beta connectin - MW of 2.1 million, with a length
of 1000 nm -it can stretch to 3000 nm!
OBiblioteka Baidu
O
O
H2N CH C CH2OH
NH CH C CH2SH
NH CH C OH CH2CNH2 O
– Ser-Cys-Asn
– Serinylcysteinylasparagine
Naturally-occurring peptides
« Peptides synthesized on the ribosome
Size of protein molecules
“Diversity of Proteins”
Could be fibrous, globular or membrane-bound
“Diversity of Proteins”
☺Polypeptides + possibly cofactors (coenzymes, prosthetic groups and metal ions), other modifications