Sandbox GGC5
From Proteopedia
(Difference between revisions)
| (8 intermediate revisions not shown.) | |||
| 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. | ||
| - | + | [[Image:beta lactam ring in antibiotics.png]] | |
| - | [[Image: | + | |
Beta Lactam Ring present in Antibiotics | 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]] | [[Image:Penicillin inhibition.svg]] | ||
Penicillin inhibition | 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. | + | 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'' |
- 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>. | ||
| - | + | <scene name='78/781193/Po4/1'>PO4 Ligand</scene> | |
- 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>. | ||
| + | <scene name='78/781193/2_zincs/1'>Zinc ions are adjacent to the phosphate to balance the charge</scene> | ||
| - | -1 | + | - 2007 hydrophobic amino acid residues <ref>DOI 10.2210/pdb3ZWF/pdb</ref>. |
| + | <scene name='78/781193/Hydrophobic_amino_acids/1'>hydrophobic amino acid properties </scene> | ||
| + | |||
| + | - 1878 polar amino acid residues <ref>DOI 10.2210/pdb3ZWF/pdb</ref>. | ||
| + | <scene name='78/781193/Polar_amino_acids/1'>polar amino acids</scene> | ||
| - | |||
- 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>. | ||
| + | <scene name='78/781193/Sodium_ion_enlarged/1'>Sodium Ion present</scene> | ||
| - | 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. | ||
</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. | ||
| - | + | == '''References''' == | |
| - | + | ||
| - | == References == | + | |
<references/> | <references/> | ||
Current revision
Contents |
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 [15]. 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 [16].
Evolutionary Considerations
Beta Lactamase protein structure is highly conserved across both prokaryotes and eukaryotes [17]. Their presence indicates that these proteins are highly adaptable, with a wide range of substrates [18]. The highly conserved nature of this structure suggests that the genetic material for beta lactamase is ancient in origin [19]. They have found early beta lactamases in deep sea sediment, before the first antibiotic was ever encountered.
References
- ↑ Tooke CL, Hinchliffe P, Bragginton EC, Colenso CK, Hirvonen VHA, Takebayashi Y, Spencer J. beta-Lactamases and beta-Lactamase Inhibitors in the 21st Century. J Mol Biol. 2019 Aug 23;431(18):3472-3500. doi: 10.1016/j.jmb.2019.04.002. Epub, 2019 Apr 5. PMID:30959050 doi:http://dx.doi.org/10.1016/j.jmb.2019.04.002
- ↑ Tooke CL, Hinchliffe P, Bragginton EC, Colenso CK, Hirvonen VHA, Takebayashi Y, Spencer J. beta-Lactamases and beta-Lactamase Inhibitors in the 21st Century. J Mol Biol. 2019 Aug 23;431(18):3472-3500. doi: 10.1016/j.jmb.2019.04.002. Epub, 2019 Apr 5. PMID:30959050 doi:http://dx.doi.org/10.1016/j.jmb.2019.04.002
- ↑ Tooke CL, Hinchliffe P, Bragginton EC, Colenso CK, Hirvonen VHA, Takebayashi Y, Spencer J. beta-Lactamases and beta-Lactamase Inhibitors in the 21st Century. J Mol Biol. 2019 Aug 23;431(18):3472-3500. doi: 10.1016/j.jmb.2019.04.002. Epub, 2019 Apr 5. PMID:30959050 doi:http://dx.doi.org/10.1016/j.jmb.2019.04.002
- ↑ https://doi.org/10.1021/cr030102i
- ↑ 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:http://dx.doi.org/10.1080/10409230701279118
- ↑ doi: https://dx.doi.org/10.2210/pdb3ZWF/pdb
- ↑ https://doi.org/10.1101/575373
- ↑ 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:http://dx.doi.org/10.1080/10409230701279118
- ↑ doi: https://dx.doi.org/10.2210/pdb3ZWF/pdb
- ↑ doi: https://dx.doi.org/10.2210/pdb3ZWF/pdb
- ↑ doi: https://dx.doi.org/10.2210/pdb3ZWF/pdb
- ↑ doi: https://dx.doi.org/10.2210/pdb3ZWF/pdb
- ↑ doi: https://dx.doi.org/10.2210/pdb3ZWF/pdb
- ↑ doi: https://dx.doi.org/10.2210/pdb3ZWF/pdb
- ↑ 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:http://dx.doi.org/10.1080/10409230701279118
- ↑ https://doi.org/10.1101/575373
- ↑ doi: https://dx.doi.org/https
- ↑ https://doi.org/10.1101/575373
- ↑ https://doi.org/10.1101/575373
[1] [2] [3] [4] [5] [6] [7] [8]
