Download Amino Acids

Chem 1152: Ch. 19
Proteins
Structures of Amino Acids
• Proteins and polypeptides are biochemical compounds
consisting of amino acids
– Chains of amino acids bonded together by peptide bonds between the
carboxyl and amino groups of adjacent amino acid residues
• Proteins
– Longer and more complex than polypeptides
– Typically folded into a globular or fibrous form
– Structure facilitates a biological function
Peptide linkages
R
R
H 3N
O
+
+
H3N
O
-
Amino acid
CH
NH
C
CH
O
R
O
R
C
CH
NH
Polypeptide
O
-
C
O
Protein
Amino Acids
•
•
•
•
•
•
•
Organic compounds with amino and carboxylate functional groups
Each AA has unique side chain (R) attached to alpha (α) carbon
Crystalline solids with high MP’s
Highly-soluble in water
Exist as dipolar, charged zwitterions (ionic form)
Exist as either L- or D- enantiomers
Almost without exception, biological organisms use only the L enantiomer
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011; Berg JM, Tymoczko JL, Stryer L, Biochemistry, 5th Edition, 2002
Amino Acids
•
20 amino acids, grouped by different properties associated with R group (residues)
http://courses.bio.indiana.edu/L104-Bonner/Sp11/imagesSp11/L12/Part1MPs.html
Formation of Polypeptides
• Polypeptides and proteins are created through formation of
peptide bonds between amino acids
– Condensation reaction
Peptide linkages
R
+
H3N
CH
NH
C
CH
O
R
O
R
C
CH
NH
Polypeptide
http://en.wikipedia.org/wiki/File:AminoacidCondensation.svg
O
C
O
-
Some Important Peptides
• Vasopressin
– Reduces the volume of urine formed in the body to retain water
• Oxytocin
– Causes contractions in smooth muscles of uterus
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011
Proteins have different levels of structure
• Primary (1°): Sequence of amino acids
– Determines 3D structure
• Secondary (2°): H-bonding interactions
between AA residues begin to produce
regular, identifiable structures
– Alpha (α) helices
– Beta (β) strands
– Random coil
• Tertiary (3°): Overall structure of single
protein in 3 dimensions
• Quaternary (4°): Assemblies of multiple
polypeptides and/or proteins
http://protein-pdb.com/2011/10/04/primary-protein-structure/
Proteins 1° Structure: The Sequence of Amino Acids
• Primary (1°): Sequence of amino acids
– Primary structure held together by peptide bonds
– Protein sequence determined by sequence of a gene in the genetic
code
– Determines 3D structure
http://protein-pdb.com/2011/10/04/primary-protein-structure/
Protein Secondary Structure
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011
Proteins 2° Structure: The α-helix
• Backbone N-H groups form H-bonds with C=O group four residues away in
sequence
• AA’s in an α helix arranged in a right-handed helix
• Each amino acid residue is rotated 100° relative to previous residue in helix
– Helix has 3.6 residues per turn
http://simplygeology.wordpress.com/tag/s-waves/
Proteins 2° Structure: The β-sheet
• Beta (β) sheets formed by H-bond connected strands
• β strands are elongated helices without helical H-bonds
• β Sheets may be parallel or antiparallel
http://www.chembio.uoguelph.ca/educmat/phy456/456lec01.htm
Proteins 2° Structure: Random Coils and Loops
• Proteins typically contain regions lacking either sheet or helical structures.
These regions may be classified as:
– Random Coils
– Loops
• Loops may perform important structural and functional roles, including:
– Connecting β strands form antiparallel sheets
– Increasing flexibility (hinge motion)
– Binding metal ions or other biomolecules to alter protein function
http://www.chembio.uoguelph.ca/educmat/phy456/456lec01.htm
Proteins 3° Structure
• Protein function determined by 3D shape
• Tertiary structure results from residue interactions:
–
–
–
–
H-bonding
Disulfide Bridges
Salt Bridges
Hydrophobic Interactions
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011
Proteins 3° Structure
• Polar and charged residues tend to be on surface of protein, exposed to
water, while hydrophobic residues tend to be buried
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011
Proteins 4° Structure
• Functional proteins may
contain two or more
polypeptide chains held
together by the same forces
that control 3° structure:
–
–
–
–
H-bonding
Disulfide Bridges
Salt Bridges
Hydrophobic Interactions
• Each chain is a subunit of
structure
• Each subunit has its own 1°, 2°
and 3° structure
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011
Proteins are Large Macromolecules
• Proteins are extremely large
– MW of glucose is 180 u, compared with 65,000 u for hemoglobin
• Proteins synthesized inside cells remain inside cells
– The presence of intracellular proteins in blood or urine can be used to test for certain diseases
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011
Protein Functions
• Catalytic Function:
– Enzymes are proteins that catalyze biological functions
• Structural function:
– Most human structural materials (excluding bone) are comprised of proteins
– Collagen (bundled helices)
• 25-35% of total protein in body
• Tendons
• ligaments
• Skin
• Cornea
• Cartilage
• Bone
• blood vessels
• gut
– Keratin (bundled helices)
• Chief constituent of hair, skin, fingernails
http://www.imb-jena.de/~rake/Bioinformatics_WEB/proteins_classification.html
Protein Functions
• Storage Function:
– Storage of small molecules or ions
– Ovalbumin
• Main protein in egg whites
• Can be broken down into amino acids for use by developing embryos
– Ferritin
• Globular complex of 24 protein subunits
• Buffers iron concentration in cells
Ovalbumin (chicken egg white)
http://www.stagleys.demon.co.uk/explorers/genesandproteins/page6.html; http://ferritin.blogspot.com/
ferritin
Protein Functions
• Protective Function:
– Protection against external foreign substances
Immunoglobulin
• Antibodies
– Very large proteins
– Combine with, and destroy viruses, bacteria
– blood clotting/Coagulation
• thrombin
– Protease responsible for platelet aggregation
and formation of fibrin
Harris, L. J., Larson, S. B., Hasel, K. W., Day, J., Greenwood, A., McPherson, A. Nature 1992, 360, 369-372; http://courses.washington.edu/conj/immune/antibody.htm;
http://www.colorado.edu/intphys/Class/IPHY3430-200/014blood.htm
Protein Functions
• Regulatory Function:
– Protein hormones
• Insulin
– Protein hormone that directs cells in the liver, muscle,
and fat to take up glucose from the blood and store it
as glycogen
– Forms hexamer bound together by Zn
Insulin
http://en.wikipedia.org/wiki/File:InsulinHexamer.jpg; Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011
Protein Functions
• Nerve impulse transmission:
– Rhodopsin
• Protein found in rods cells of eye retina
– Converts light events into nerve impulses sent to the
brain
http://cherfan2010biology12assessment.wikispaces.com/The+Retina
Protein Functions
• Movement function:
– Proteins involved in muscle contraction
• Myosin
• Actin
http://www.sigmaaldrich.com/life-science/metabolomics/enzyme-explorer/learning-center/structural-proteins/actin.html
Protein Functions
• Transport function:
– Transport ions or molecules throughout the body
• Serum albumin: Transports fatty acids between fat and other tissues
• Hemoglobin: Transports O2 from lungs to other tissues (e.g., muscles)
• Transferrin: Transports iron in blood plasma
Serum albumin
hemoglobin
transferrin
http://en.wikipedia.org/ ; http://www.pdb.org/pdb/101/motm.do?momID=37
Protein Classifications
Based on structural shape
• Fibrous Proteins
– Comprised of long stringlike molecules that can wrap around each other to form fibers
– Usually insoluble in water
– Major components of connective tissues (e.g., collagen, keratin)
• Globular proteins
– Spherical
– Usually water soluble
– May be moved through the body (e.g., hemoglobin, transferrin)
Based on composition
• Simple Proteins
– Contain only amino acid residues
• Conjugated Proteins
– Contain amino acid residues and other organic or inorganic components (i.e., prosthetic
groups)
• Lipoproteins
• Glycoproteins
• metalloproteins
http://www.sigmaaldrich.com/life-science/metabolomics/enzyme-explorer/learning-center/structural-proteins/actin.html