# Structural Biochemistry/Catalytic Strategies

Enzymes are proteins that catalyze a reaction by stabilizing the transition state and therefore, lowering the activation energy of the reaction. To achieve this, enzymes use different classes of reactions known as catalytic strategies. Four classes of enzymes are used in catalytic strategies are: - Serine Proteases: example of catalytic mechanism of chymotrypsin - Carbonic Anhydrase: make a fast reaction faster Carbonic anhydrases dehydrate HCO3- in blood to form CO2 for exhalation as the blood passes through the lungs. - Restriction Endonucleases (BamHI): Bam HI: is used for DNA cleavage reaction. This enzyme recognizes particular base sequences, recognition sites, in target DNA and cleave DNA at a defined positions. I co-crystallized the complex BamHI-DNA with a divalent cations BamHI binding to nonspecific DNA forms an electrostatic traps that allows sliding along DNA. Catalytic Mechanism: Pre-reactive state (Glutamic acid 113 acts as general base removing a proton from water molecule)
- Nucleoside Monophosphate Kinase NMP kinase is enzyme that aids in transferring the phosphoryl group at the end of a nucleoside triphosphate to the phosphoryl group that is on a nucleoside monophosphate NMP + ATP --> NDP + ADP
The strategies used to catalyze a reaction are:
Whereas most enzymes simply have an active site that changes the shape of a substrate, in covalent catalysis, the enzymes (or cofactors) covalently bond to the substrate as the first step. The active sites contain a reactive group, usually a nucleophile, that forms a covalent bond with the substrate. Then, the enzyme goes through a mechanism, eventually breaking down the substrate and reforming itself. Chymotrypsin, for example, can catalyze reactions by utilizing covalent modification. It can employ a serine residue as a nucleophile to attract the unreactive carbonyl group of a substrate.
Other proteases like chymotrypsin, such as trypsin, can use a catalytic triad (containing aspartate, histidine and serine residues) to activate enzymatic activity and break peptide bonds. Proteases usually involves a nucleophile that attracts a peptide carbonyl group. Cystein proteases is activated by histidine to attack the carbonyl group. Aspartyl proteases is activated by aspartate pairs, which exists in deprotonated and protonated forms to attack a water molecule and carbonyl group, respectively. Metalloproteases is activated by a bound metal ion (usually zinc) to activate the water molecule, which acts as a nucleophile to attack the peptide carbonyl group.
These enzymes generally use a molecule other than water to donate or accept protons as a nucleophile. An example is that of a Zinc ion - Histidine complex in carbonic anhydrase that breaks down the H2CO4 into hydrogen ions and bicarbonate ions. The zinc attracts a water molecule which then deprotonates. The oxygen acts as a nucleophile and attacks a carbon dioxide molecule to create a complicated coordination complex. Another then replaces the complex, releasing the bicarbonate ion.
The close proximity of two substrates can increase the rate of reaction between the two. Generally, when two molecules combine to become one, entropy decreases. An enzyme that brings the two molecules together decreases the entropy. This increase in rate is similar to increasing the concentration of the reactants. However, catalysis by approximation generally increases the reaction rate more than simply increasing the concentration of the reactants since the enzyme generally makes the reaction pseudo-intramolecular.
Metal ions can directly facilitate the formation of bonds. Because they are electrophillic, they can also act to stabilize the charges on the intermediates in the reaction.
The type of strategy that is employed is based on the enzyme's structural properties and the reaction that the enzyme will catalyze. Many times a combination of strategies is used to in catalytic reactions.