Sandbox GGC5: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 2: | Line 2: | ||
<StructureSection load='3ZWF' size='340' side='right' caption='tRNAse Z Metallo-Beta Lactamase (homosapien)' scene=''> | <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. | 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'''== | ||
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. | ||
| Line 18: | Line 18: | ||
https://en.wikipedia.org/wiki/%CE%92-lactam_antibiotic#/media/File:Penicillin_inhibition.svg | 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. | 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)'''== | ||
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'''== | ||
Macromolecules: | Macromolecules: | ||
Two chains (A,B) of Zinc phosphodiesterase ELAC Protein 1 <ref>DOI 10.2210/pdb3ZWF/pdb</ref>. | Two chains (A,B) of Zinc phosphodiesterase ELAC Protein 1 <ref>DOI 10.2210/pdb3ZWF/pdb</ref>. | ||
Unique Ligands | ''Unique Ligands'' | ||
| Line 50: | Line 50: | ||
</StructureSection> | </StructureSection> | ||
== | =='''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>. | ||
== Evolutionary Considerations == | == '''Evolutionary Considerations''' == | ||
Beta Lactamase protein structure is highly conserved across both prokaryotes and eukaryotes <ref>doi: https://doi.org/10.1101/819797</ref>. Their presence indicates that these proteins are highly adaptable, with a wide range of substrates <ref>https://doi.org/10.1101/575373</ref>. The highly conserved nature of this structure suggests that the genetic material for beta lactamase is ancient in origin <ref>https://doi.org/10.1101/575373</ref>. They have found early beta lactamases in deep sea sediment, before the first antibiotic was ever encountered. | Beta Lactamase protein structure is highly conserved across both prokaryotes and eukaryotes <ref>doi: https://doi.org/10.1101/819797</ref>. Their presence indicates that these proteins are highly adaptable, with a wide range of substrates <ref>https://doi.org/10.1101/575373</ref>. The highly conserved nature of this structure suggests that the genetic material for beta lactamase is ancient in origin <ref>https://doi.org/10.1101/575373</ref>. They have found early beta lactamases in deep sea sediment, before the first antibiotic was ever encountered. | ||
| Line 61: | Line 61: | ||
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. | ||
== References == | == '''References''' == | ||
<references/> | <references/> | ||
Revision as of 15:43, 28 April 2021
Beta Lactamase
| ||||||||||||
Disease
If there are mutations in the tRNase Z metallo-beta lactamases, these enzymes have been implicated in several diseases including prostate cancer [1]. 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 [2].
Evolutionary Considerations
Beta Lactamase protein structure is highly conserved across both prokaryotes and eukaryotes [3]. Their presence indicates that these proteins are highly adaptable, with a wide range of substrates [4]. The highly conserved nature of this structure suggests that the genetic material for beta lactamase is ancient in origin [5]. They have found early beta lactamases in deep sea sediment, before the first antibiotic was ever encountered.
This is a sample scene created with SAT to color by Group, and another to make a transparent representation of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
References
- ↑ Dominski Z. Nucleases of the metallo-beta-lactamase family and their role in DNA and RNA metabolism. Crit Rev Biochem Mol Biol. 2007 Mar-Apr;42(2):67-93. doi:, 10.1080/10409230701279118. PMID:17453916 doi:https://dx.doi.org/10.1080/10409230701279118
- ↑ https://doi.org/10.1101/575373
- ↑ doi: https://dx.doi.org/10.1101/819797
- ↑ https://doi.org/10.1101/575373
- ↑ https://doi.org/10.1101/575373
[1] [2] [3] [4] [5] [6] [7] [8]
