Enzymes

Specificity of Enzymes

Specificity of Enzymes

Specificity of Enzymes

Enzymes are specific to particular reactions. There are 4 types of specificity – absolute, group, linkage, and stereochemical. Not all enzymes work on all substrates.

Absolute Specificity

Absolute specificity means that one and only one substrate will fit with a particular enzyme.

Active Site

Substrate

Active Site + Substrate

The enzyme glutamate dehydrogase (1BGV.pdb) will catalyze only the removal of the nitrogen group from glutamate- NOT any other amino acid.  It has absolute specificity.

PencilWhat atoms/groups are in the active site of this enzyme?

PencilWhat atoms are in the substrate?

PencilWhat possible interactions could be occurring between the substrate and active site?

PencilWhy do you think that - speculate - this enzyme has absolute specificity based on the structure that you see?

PencilWhat would be an advantage and a disadvantage of absolute specificity?

Group Specificity

Group specificity means that an enzyme will catalyze a reaction on a function group of a variety of molecules (for instance, cleaving an alcohol group or working only on aldohexose sugars).

Note the multiple buttons for this next enzyme because it is so large. It actually forms a sphere when all 24 subunits are pictured. You are only seeing part of it because of the large size.

The enzyme sulfur oxygenase reductase (2CB2.pdb) catalyzes the reduction of inorganic sulfur compounds and elemental sulfur to sulfate and is a major part of the global sulfur cycle. This enzyme has a group specificity of only sulfur compounds.

Protein Overview - Sulfur Oxygenase Reductase

The reaction is as follows:

groupspec

Here the active site for the sulfur substrate is composed of a cysteine persulfide (flashes lime green) and an iron atom (flashes light blue) held by a 2-His-1-carboxylate facial triad (the CPK amino acids). In this case, the 2-His-1-carboxylate facial triad is composed of 2 histidines and 1 glutamate.

Multiple Subunits - Each with an Identical Active Site

PencilWhat atoms of the enzyme/amino acid residues are probably holding the cysteine and persulfide?

Let's explore the active site in more detail. There is not a substrate pictured in the active site; the researchers are not yet able to crystallize the substance.

Active Site in Detail

PencilThe iron is necessary for this reaction to occur. Looking at the name of the enzyme and remembering what you learned in general chemistry - what type of reactions are occurring in this enzyme?

PencilWhat would be an advantage and a disadvantage of group specificity?

Linkage Specificity

Linkage specificity means that enzymes break one type of bond.

Active Site

Substrate

Active Site + Substrate

PencilWhat atoms/groups are in the active site of this enzyme?

PencilWhat atoms are in the substrate?

PencilWhat possible interactions could be occurring between the substrate and the active site?

Here, we can see the active site and the substrate of Fructose 1,6-Bisphosphate Aldolase (4ALD.pdb), an enzyme that is part of the glycolytic pathway. The substrate is fructose 1,6-bisphosphate, and a specific bond is broken to produce dihydroxyacetone phosphate and glyceraldehyde-3-phosphate.

Click the next button to see which bond is cleaved to produce the product.

Linkage Specificity

Below is the reaction:

linkagespec

PencilGive another example of linkage specificity that we learned about when studying carbohydrates. (There are 2).

PencilWhat would be an advantage and a disadvantage of linkage specificity?

Stereochemical Specificity

Stereochemical specificity means that enzymes will only work on one enantiomer. For example they could break D-sugars but not L-sugars. This enzyme is D-Lactate Dehydogenase complexed with D-lactic acid (3KB6.pdb).

Active Site

Substrate

Active Site + Substrate

The substrate is D-lactic acid, which flashes in cyan.

PencilDo you think that the other enantiomer, L-lactic acid, would fit in this enzyme's active site? Why or why not?

PencilDo you think there are a lot of these types of enzymes? Why?

PencilWhat would be an advantage and a disadvantage of stereochemical specificity?

PencilWrite a complete sentence for each type of specificity.

3-dimensional Jmol Display

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