Enzymes SADIA SAYED

Enzymes are proteins  All enzymes are proteins  Strings of amino acids folding up into distinct structures  The properties of a protein (Enzyme) are largely determined by its three-dimensional structure- Folding  There are several levels of protein folding 1. Primary 2. Secondary 3. Tertiary 4. Quaternary

Water, water, everywhere  The fluid of life  Properties of water: 1. Ionic bonding between O and H atoms 2. Asymmetric charge distribution- Polar 3. Forms Hydrogen bonding with other water molecules and polar solutes 4. Repels hydrophobic molecules

Primary structure of proteins  A description of all covalent bonds (Mainly peptide bonds and disulfide bonds) linking amino acid residues in a polypeptide chain  The most important element of primary structure is the sequence of amino acid residues  Each protein has a distinctive number and sequence of amino acid residues  The function of a protein depends mainly on its amino acid sequence (Primary structure) which ultimately governs its folding into higher order structures

Secondary structure of proteins  Defined as the local conformation of its backbone  Particularly stable arrangements of amino acid residues giving rise to recurring structural patterns: Helices, pleated sheets, and turns  Stabilized largely by weak non-covalent interactions  α helix: The polypeptide backbone is tightly wound around an imaginary axis drawn Iongitudinally through the middle of the helix, and the R groups of the amino acid residues protrude outward from the helical backbone. The repeating unit is a single turn of the helix, which extends about 5.4 A along the long axis, slightly greater than the periodicity. The amino acid residues in the prototypical α helix have conformations with φ = -57 ˚ and ψ = -47 ˚, and each helical turn includes 3.6 amino acid residues

Secondary structure of proteins  β sheet: The backbone of the polypeptide chain is extended into a zigzag form, arranged side by side to create a structure resembling a series of pleats. Hydrogen bonds form between adjacent segments of polypeptide chain. The individual segments that form a β sheet are usually nearby on the polypeptide chain, but can also be quite distant from each other in the linear sequence of the polypeptide; they may even be in different polypeptide chains. The R groups of adjacent amino acids protrude from the zigzag structure in opposite directions, the adjacent polypeptide chains in a β sheet can be either parallel or antiparallel (having the same or opposite amino-to-carboxyl orientations, respectively

Secondary structure of proteins  β turn: Connects the ends of two adjacent segments of an antiparallel β sheet. The structure is a 180 ˚ turn involving four amino acid residues, with the carbonyl oxygen of the first residue forming a hydrogen bond with the amino-group hydrogen of the fourth  Other less common structures also prevail

β turn

Tertiary structure of proteins  Describes all aspects of the three-dimensional folding of a polypeptide  Two major groups: 1. Fibrous proteins: Polypeptide chains arranged in long strands or sheets, usually consist largely of a single type of secondary structure, and their tertiary structure is relatively simple. Structures that provide support, shape, and external protection to vertebrates are made of fibrous proteins 2. Globular proteins: Polypeptide chains folded into a spherical or globular shape. Globular proteins often contain several types of secondary structure. Most enzymes and regulatory proteins are globular proteins

QUATERNARY STRUCTURE OF PROTEINS  When a protein has two or more polypeptide subunits  Protein quaternary structure ranges from simple dimers to large complexes  Some multimeric proteins have a repeated unit consisting of a single subunit or a group of subunits, or protomer

SPECIFICiTY?  Emil Fischer’s discovery, in 1894, that glycolytic enzymes can distinguish between stereoisomeric sugars led to the formulation of his lock-and-key hypothesis: The specificity of an enzyme (the lock) for its substrate (the key) arises from their geometrically complementary shapes  The noncovalent forces through which substrates and other molecules bind to enzymes are similar in character to the forces that dictate the conformations of the proteins themselves= Both involve van der Waals, electrostatic, hydrogen bonding, and hydrophobic interactions  A substrate-binding site consists of an indentation or cleft on the surface of an enzyme molecule that is 1. Complementary in shape to the substrate (Geometric complementarity) 2. The amino acid residues that form the binding site are arranged to interact specifically with the substrate in an attractive manner (Electronic complementarity)

Specificity  Four distinct types of specificity: 1. Stereochemical specificity: The enzyme will act on a particular steric or optical isomer 2. Absolute specificity: The enzyme will catalyze only one reaction 3. Group specificity: The enzyme will act only on molecules that have specific functional groups, such as amino, phosphate and methyl groups 4. Linkage specificity: The enzyme will act on a particular type of chemical bond regardless of the rest of the molecular structure

stereospecificty  Enzymes are highly specific both in binding chiral substrates and in catalyzing their reactions  Enzymes are absolutely stereospecific in the reactions they catalyze  Consider the reaction of yeast alcohol dehydorgenase

Geometric Specificity  A substrate of the wrong chirality will not fit into an enzymatic binding site  Most enzymes are quite selective about the identities of the chemical groups on their substrates. Indeed, such geometric specificity is a more stringent requirement than is stereospecificity  Enzymes vary considerably in their degree of geometric specificity.  YADH catalyzes the oxidation of small primary and secondary alcohols to their corresponding aldehydes or ketones but none so efficiently as that of ethanol. Methanol and isopropanol, are oxidized by YADH at rates that are, respectively, 25-fold and 2.5-fold slower than that for ethanol. Similarly, NADP+, does not bind to YADH