Sandbox GGC5: Difference between revisions
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==Beta Lactamase == | ==""Beta Lactamase"" == | ||
<StructureSection load=' | <StructureSection load='3ZWF' size='340' side='right' caption='tRNAse Z Metallo-Beta Lactamase (homosapien)' scene=''> | ||
Beta Lactamase is a highly conserved enzyme in both prokaryotes and eukaryotes. In prokaryotes, it gives bacteria such as E.Coli antibiotic resistance. In eukaryotes, it acts as exo and endonucleases to regulate transcription activity. | |||
==""Background Information""== | |||
== Background Information== | |||
There are several classes of antibiotics, including cephalosporin and penicillin <ref>doi: 10.1016/j.jmb.2019.04.002</ref>. Some common examples of specific drugs in these classes include cefazolin, cefadroxil, penicillin, ampicillin, and methicillin <ref>doi: 10.1016/j.jmb.2019.04.002</ref>. These antibiotics function by preventing bacteria from forming their cell wall, regardless if the bacteria are gram positive or gram negative <ref>doi: 10.1016/j.jmb.2019.04.002</ref>. These antibiotics all contain a beta-lactam ring <ref>https://doi.org/10.1021/cr030102i</ref>. | There are several classes of antibiotics, including cephalosporin and penicillin <ref>doi: 10.1016/j.jmb.2019.04.002</ref>. Some common examples of specific drugs in these classes include cefazolin, cefadroxil, penicillin, ampicillin, and methicillin <ref>doi: 10.1016/j.jmb.2019.04.002</ref>. These antibiotics function by preventing bacteria from forming their cell wall, regardless if the bacteria are gram positive or gram negative <ref>doi: 10.1016/j.jmb.2019.04.002</ref>. These antibiotics all contain a beta-lactam ring <ref>https://doi.org/10.1021/cr030102i</ref>. | ||
Inside of the gram positive or gram negative bacteria, there is a protein called the penicillin binding protein. The penicillin binding proteins (PBPs) are what help the peptidoglycan walls to form by linking NAG and NAM chains together. The beta-lactam ring fits particularly well into the PBP, which is how antibiotics like penicillin prevent bacteria from synthesizing its cell wall. | Inside of the gram positive or gram negative bacteria, there is a protein called the penicillin binding protein. The penicillin binding proteins (PBPs) are what help the peptidoglycan walls to form by linking NAG and NAM chains together. The beta-lactam ring fits particularly well into the PBP, which is how antibiotics like penicillin prevent bacteria from synthesizing its cell wall. | ||
== Mechanism of Antibiotic Beta Lactam Ring Resistance == | |||
[[Image: Beta-lactam antibiotics example 1.svg]] | |||
Beta Lactam Ring present in Antibiotics | |||
https://en.wikipedia.org/wiki/%CE%92-lactam_antibiotic#/media/File:Beta-lactam_antibiotics_example_1.svg | |||
[[Image:Penicillin inhibition.svg]] | |||
Penicillin inhibition | |||
https://en.wikipedia.org/wiki/%CE%92-lactam_antibiotic#/media/File:Penicillin_inhibition.svg | |||
== "" Mechanism of Antibiotic Beta Lactam Ring Resistance "" == | |||
Bacteria such as E. Coli make and excrete an enzyme called beta lactamase <ref>DOI: 10.1080/10409230701279118</ref>. Bacteria can become resistant to antibiotics that contain lactam rings when the B-lactamase enzyme attacks the beta lactam ring (classified as a hydrolase). Once the beta lactam ring is sliced open, it is no longer functional <ref> DOI 10.2210/pdb3ZWF/pdb </ref>. | Bacteria such as E. Coli make and excrete an enzyme called beta lactamase <ref>DOI: 10.1080/10409230701279118</ref>. Bacteria can become resistant to antibiotics that contain lactam rings when the B-lactamase enzyme attacks the beta lactam ring (classified as a hydrolase). Once the beta lactam ring is sliced open, it is no longer functional <ref> DOI 10.2210/pdb3ZWF/pdb </ref>. | ||
== Beta Lactamase in Humans (PDB: 3ZWF) == | == ""Beta Lactamase in Humans (PDB: 3ZWF)"" == | ||
In order to make mature tRNAs, first they have to be processed <ref>https://doi.org/10.1101/575373</ref>. The enzyme that does tRNA processing is called TRNase Z. In humans, the form of beta lactamase formed uses a zinc-dependent mechanism, noted as metallo-beta lactamase <ref>DOI: 10.1080/10409230701279118</ref>. These enzymes in humans function to regulate nuclear activity, providing exo and endonuclease activity. | In order to make mature tRNAs, first they have to be processed <ref>https://doi.org/10.1101/575373</ref>. The enzyme that does tRNA processing is called TRNase Z. In humans, the form of beta lactamase formed uses a zinc-dependent mechanism, noted as metallo-beta lactamase <ref>DOI: 10.1080/10409230701279118</ref>. These enzymes in humans function to regulate nuclear activity, providing exo and endonuclease activity. | ||
== Structural highlights == | == ""Structural highlights"" == | ||
Macromolecules: | Macromolecules: | ||
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Unique Ligands | Unique Ligands | ||
- Phosphate (PO4) ligand on chains A and B of Zinc phosphodiesterase ELAC Protein 1 <ref>DOI 10.2210/pdb3ZWF/pdb</ref>. | - Phosphate (PO4) ligand on chains A and B of Zinc phosphodiesterase ELAC Protein 1 <ref>DOI 10.2210/pdb3ZWF/pdb</ref>. | ||
- Zinc (Zn) ligand on chains A and B of Zinc phosphodiesterase ELAC Protein 1 <ref>DOI 10.2210/pdb3ZWF/pdb</ref>. | - Zinc (Zn) ligand on chains A and B of Zinc phosphodiesterase ELAC Protein 1 <ref>DOI 10.2210/pdb3ZWF/pdb</ref>. | ||
-1,2 Ethanediol (EDO) ligand on chains A and B of Zinc phosphodiesterase ELAC Protein 1 <ref>DOI 10.2210/pdb3ZWF/pdb</ref>. | |||
-1,2 Ethanediol (EDO) ligand on chains A and B of Zinc phosphodiesterase ELAC Protein 1 <ref>DOI 10.2210/pdb3ZWF/pdb</ref>. | |||
- Sodium (Na+) ion on chain B of Zinc phosphodiesterase ELAC Protein 1 <ref>DOI 10.2210/pdb3ZWF/pdb</ref>. | - Sodium (Na+) ion on chain B of Zinc phosphodiesterase ELAC Protein 1 <ref>DOI 10.2210/pdb3ZWF/pdb</ref>. | ||
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</StructureSection> | </StructureSection> | ||
== Disease == | == "" Disease "" == | ||
If there are mutations in the tRNase Z metallo-beta lactamases, these enzymes have been implicated in several diseases including prostate cancer <ref>DOI: 10.1080/10409230701279118</ref>. While there is still much to learn about how these lactamases work inter-connectedly with other enzymes, research suggests that metallo-beta lactamases function as cleavage and polyadenylation factors <ref>https://doi.org/10.1101/575373</ref>. | If there are mutations in the tRNase Z metallo-beta lactamases, these enzymes have been implicated in several diseases including prostate cancer <ref>DOI: 10.1080/10409230701279118</ref>. While there is still much to learn about how these lactamases work inter-connectedly with other enzymes, research suggests that metallo-beta lactamases function as cleavage and polyadenylation factors <ref>https://doi.org/10.1101/575373</ref>. | ||
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== References == | == References == | ||
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