Sandbox Reserved 994: Difference between revisions

Line 27:

There are three catalytic residues involved in the hydrolysis of β-lactam antibiotics. Serine-81 is the catalytic serine, which performs a nucleophilic attack on the β-lactam ring after being deprotonated by the carboxylated lysine-84 (KCX84). This carboxylated lysine is formed by CO2 in the environment engaging in unfavorable interactions with the hydrophobic pocket of OXA-24, so it carboxylates Lysine-84 (A).

There are three catalytic residues involved in the hydrolysis of β-lactam antibiotics. Serine-81 is the catalytic serine, which performs a nucleophilic attack on the β-lactam ring after being deprotonated by the carboxylated lysine-84 (KCX84). This carboxylated lysine is formed by CO2 in the environment engaging in unfavorable interactions with the hydrophobic pocket of OXA-24, so it carboxylates Lysine-84 (A).<ref name="Leonard" />

The second step (B) forms a high energy intermediate. The cyclic amide from the β-lactam deprotonates Serine-128 (S128), which proceeds to deprotonate the amine on KCX84, which deprotonates the carboxylate group. This high energy intermediate resolves to form the stable acyl-enzyme intermediate.

The second step (B) forms a high energy intermediate. The cyclic amide from the β-lactam deprotonates Serine-128 (S128), which proceeds to deprotonate the amine on KCX84, which deprotonates the carboxylate group. This high energy intermediate resolves to form the stable acyl-enzyme intermediate.<ref name="Leonard" />

The third step (C) proceeds with the use of a catalytic water, which is deprotonated by KCX84. The water now can mount a nucleophilic attack on the ester linkage connecting S81 and the hydrolyzed β-lactam. This forms a high energy dissociation intermediate, where S81 is released by a mechanism, which has not quite yet been determined. It is suspected that it deprotonates KCX84, but this has not yet been confirmed.

The third step (C) proceeds with the use of a catalytic water, which is deprotonated by KCX84. The water now can mount a nucleophilic attack on the ester linkage connecting S81 and the hydrolyzed β-lactam. This forms a high energy dissociation intermediate, where S81 is released by a mechanism, which has not quite yet been determined. It is suspected that it deprotonates KCX84, but this has not yet been confirmed.<ref name="Leonard" />

In step four (D), The enzyme is successfully regenerated and the hydrolyzed β-lactam antibiotic is released back into solution. OXA-24 is now free to hydrolyze another substrate and the antibiotic has been rendered useless.

In step four (D), The enzyme is successfully regenerated and the hydrolyzed β-lactam antibiotic is released back into solution. OXA-24 is now free to hydrolyze another substrate and the antibiotic has been rendered useless.<ref name="Leonard" />

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

Sandbox Reserved 994: Difference between revisions

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@@ Line 27: / Line 27: @@
-There are three catalytic residues involved in the hydrolysis of β-lactam antibiotics. Serine-81 is the catalytic serine, which performs a nucleophilic attack on the β-lactam ring after being deprotonated by the carboxylated lysine-84 (KCX84). This carboxylated lysine is formed by CO2 in the environment engaging in unfavorable interactions with the hydrophobic pocket of OXA-24, so it carboxylates Lysine-84 (A).
+There are three catalytic residues involved in the hydrolysis of β-lactam antibiotics. Serine-81 is the catalytic serine, which performs a nucleophilic attack on the β-lactam ring after being deprotonated by the carboxylated lysine-84 (KCX84). This carboxylated lysine is formed by CO2 in the environment engaging in unfavorable interactions with the hydrophobic pocket of OXA-24, so it carboxylates Lysine-84 (A).<ref name="Leonard" />
-The second step (B) forms a high energy intermediate. The cyclic amide from the β-lactam deprotonates Serine-128 (S128), which proceeds to deprotonate the amine on KCX84, which deprotonates the carboxylate group. This high energy intermediate resolves to form the stable acyl-enzyme intermediate.
+The second step (B) forms a high energy intermediate. The cyclic amide from the β-lactam deprotonates Serine-128 (S128), which proceeds to deprotonate the amine on KCX84, which deprotonates the carboxylate group. This high energy intermediate resolves to form the stable acyl-enzyme intermediate.<ref name="Leonard" />
-The third step (C) proceeds with the use of a catalytic water, which is deprotonated by KCX84. The water now can mount a nucleophilic attack on the ester linkage connecting S81 and the hydrolyzed β-lactam. This forms a high energy dissociation intermediate, where S81 is released by a mechanism, which has not quite yet been determined. It is suspected that it deprotonates KCX84, but this has not yet been confirmed.
+The third step (C) proceeds with the use of a catalytic water, which is deprotonated by KCX84. The water now can mount a nucleophilic attack on the ester linkage connecting S81 and the hydrolyzed β-lactam. This forms a high energy dissociation intermediate, where S81 is released by a mechanism, which has not quite yet been determined. It is suspected that it deprotonates KCX84, but this has not yet been confirmed.<ref name="Leonard" />
-In step four (D), The enzyme is successfully regenerated and the hydrolyzed β-lactam antibiotic is released back into solution. OXA-24 is now free to hydrolyze another substrate and the antibiotic has been rendered useless.
+In step four (D), The enzyme is successfully regenerated and the hydrolyzed β-lactam antibiotic is released back into solution. OXA-24 is now free to hydrolyze another substrate and the antibiotic has been rendered useless.<ref name="Leonard" />
 This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.