Oxyanion hole: Difference between revisions

Latest revision as of 06:12, 16 February 2025

An article about the oxyanion hole in serine proteases

Oxyanion hole[edit]

The oxyanion hole is a structural feature found in the active site of serine proteases, which are a class of proteolytic enzymes. This feature plays a crucial role in stabilizing the transition state of the substrate during the catalytic process.

Structure[edit]

The oxyanion hole is typically formed by the backbone amides of the enzyme. In serine proteases, it is composed of the amide groups of the peptide backbone, which are positioned to form hydrogen bonds with the negatively charged oxygen atom of the tetrahedral intermediate. This intermediate is formed during the nucleophilic attack of the serine residue on the carbonyl carbon of the substrate.

Function[edit]

The primary function of the oxyanion hole is to stabilize the high-energy transition state of the substrate. By providing hydrogen bonds to the negatively charged oxygen, the oxyanion hole lowers the activation energy required for the reaction to proceed. This stabilization is crucial for the catalytic efficiency of serine proteases.

Mechanism[edit]

During the catalytic cycle of serine proteases, the substrate binds to the active site, positioning the scissile bond near the catalytic triad, which typically consists of serine, histidine, and aspartate residues. The serine residue acts as a nucleophile, attacking the carbonyl carbon of the substrate, leading to the formation of a tetrahedral intermediate. The oxyanion hole stabilizes this intermediate by forming hydrogen bonds with the negatively charged oxygen atom.

Examples[edit]

Serine proteases such as trypsin, chymotrypsin, and elastase all contain oxyanion holes that are essential for their catalytic activity. These enzymes are involved in various physiological processes, including digestion and blood coagulation.

Related pages[edit]

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-'''Oxyanion hole''' is a structural feature found in [[enzyme|enzymes]] that stabilizes the transition state of a [[substrate (chemistry)|substrate]] during [[catalysis]]. It is typically a pocket or groove in the enzyme where an [[oxygen]] atom of the substrate can form [[hydrogen bond|hydrogen bonds]] with the enzyme, thus stabilizing the negative charge on the oxygen atom. This stabilization of the transition state lowers the [[activation energy]] of the reaction, increasing the rate of the reaction.
+{{Short description|An article about the oxyanion hole in serine proteases}}
-==Structure and Function==
+==Oxyanion hole==
+The '''oxyanion hole''' is a structural feature found in the active site of [[serine proteases]], which are a class of [[proteolytic enzymes]]. This feature plays a crucial role in stabilizing the transition state of the substrate during the catalytic process.
-The oxyanion hole is typically formed by the backbone [[amino acid|amino acids]] of the enzyme, often [[glycine]] or [[cysteine]]. These amino acids have small side chains, allowing the oxygen atom of the substrate to come into close proximity with the backbone [[amide]] groups. The amide groups can then form hydrogen bonds with the oxygen atom, stabilizing the negative charge.
+[[File:Serine_protease_oxyanion_hole.png|thumb|right|Diagram of a serine protease oxyanion hole.]]
-The oxyanion hole plays a crucial role in the mechanism of many enzymes, including [[serine protease|serine proteases]], [[thiolase]], and [[carboxypeptidase]]. In these enzymes, the oxyanion hole stabilizes the transition state of the substrate, facilitating the breakdown or formation of [[covalent bond|covalent bonds]].
+===Structure===
+The oxyanion hole is typically formed by the backbone amides of the enzyme. In serine proteases, it is composed of the amide groups of the peptide backbone, which are positioned to form hydrogen bonds with the negatively charged oxygen atom of the tetrahedral intermediate. This intermediate is formed during the nucleophilic attack of the serine residue on the carbonyl carbon of the substrate.
-==Examples==
+===Function===
+The primary function of the oxyanion hole is to stabilize the high-energy transition state of the substrate. By providing hydrogen bonds to the negatively charged oxygen, the oxyanion hole lowers the activation energy required for the reaction to proceed. This stabilization is crucial for the catalytic efficiency of serine proteases.
-One of the most well-studied examples of an oxyanion hole is in the serine proteases, a family of enzymes that includes [[trypsin]], [[chymotrypsin]], and [[elastase]]. In these enzymes, the oxyanion hole is formed by two glycine residues, and it stabilizes the transition state of the peptide bond being cleaved.
+===Mechanism===
+During the catalytic cycle of serine proteases, the substrate binds to the active site, positioning the scissile bond near the catalytic triad, which typically consists of [[serine]], [[histidine]], and [[aspartate]] residues. The serine residue acts as a nucleophile, attacking the carbonyl carbon of the substrate, leading to the formation of a tetrahedral intermediate. The oxyanion hole stabilizes this intermediate by forming hydrogen bonds with the negatively charged oxygen atom.
-Another example is thiolase, an enzyme involved in [[fatty acid metabolism]]. In thiolase, the oxyanion hole is formed by a cysteine and an adjacent amino acid, and it stabilizes the transition state of the thioester bond being cleaved.
+===Examples===
+Serine proteases such as [[trypsin]], [[chymotrypsin]], and [[elastase]] all contain oxyanion holes that are essential for their catalytic activity. These enzymes are involved in various physiological processes, including digestion and blood coagulation.
-==See also==
+==Related pages==
+* [[Serine protease]]
+* [[Catalytic triad]]
+* [[Enzyme kinetics]]
+* [[Protease]]
-* [[Enzyme catalysis]]
+[[Category:Enzymes]]
-* [[Transition state theory]]
+[[Category:Proteases]]
-* [[Active site]]
+[[Category:Enzyme catalysis]]
-[[Category:Enzyme kinetics]]
-[[Category:Protein structure]]
-[[Category:Biochemistry]]
-{{biochem-stub}}