Sandbox Reserved 994: Difference between revisions
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== Structure == | == Structure == | ||
The active site of OXA-24 is characterized by a hydrophobic pocket, which is representative of Class D β-lactamases as a whole, and a disulfide bridge. The mechanism of attack is through the use of three catalytic residues: Serine-81, Carboxylated Lysine-84, and Serine-115. | |||
== Hydrolysis Mechanism == | == Hydrolysis Mechanism == | ||
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<scene name='69/691536/Closeupdrug/1'>close up</scene><ref>PMID: 10817708</ref> | <scene name='69/691536/Closeupdrug/1'>close up</scene><ref>PMID: 10817708</ref> | ||
== | == Mechanistic Activity == | ||
There are three catalytic residues involved in the hydrolysis of β-lactam antibiotics. Serine-81 (S81) is the catalytic serine, which preforms 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. | |||
The second step forms a high energy intermediate, where protons are shifted around the newly-formed complex. 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 third step 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. | |||
In step 4, 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. | |||
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. | 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. | ||
