Sandbox GGC5: Difference between revisions

Latest revision as of 19:52, 28 April 2021

Beta Lactamase

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 ^[1]. Some common examples of specific drugs in these classes include cefazolin, cefadroxil, penicillin, ampicillin, and methicillin ^[2]. These antibiotics function by preventing bacteria from forming their cell wall, regardless if the bacteria are gram positive or gram negative ^[3]. These antibiotics all contain a beta-lactam ring ^[4]. 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.

File:Beta lactam ring in antibiotics.png

Beta Lactam Ring present in Antibiotics

File:Penicillin inhibition.svg

Penicillin inhibition

Mechanism of Antibiotic Beta Lactam Ring Resistance

Bacteria such as E. coli make and excrete an enzyme called beta lactamase ^[5]. 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 ^[6].

Beta Lactamase in Humans (PDB: 3ZWF)

In order to make mature tRNAs, first they have to be processed ^[7]. 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 ^[8]. These enzymes in humans function to regulate nuclear activity, providing exo and endonuclease activity.

Structural highlights

Macromolecules: Two chains (A,B) of Zinc phosphodiesterase ELAC Protein 1 ^[9].

Unique Ligands

- Phosphate (PO4) ligand on chains A and B of Zinc phosphodiesterase ELAC Protein 1 ^[10].

PO4 Ligand

- Zinc (Zn) ligand on chains A and B of Zinc phosphodiesterase ELAC Protein 1 ^[11].

Zinc ions are adjacent to the phosphate to balance the charge

- 2007 hydrophobic amino acid residues ^[12].

hydrophobic amino acid properties

- 1878 polar amino acid residues ^[13].

polar amino acids

- Sodium (Na+) ion on chain B of Zinc phosphodiesterase ELAC Protein 1 ^[14].

Sodium Ion present

↑ 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:https://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:https://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:https://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:https://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:https://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

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.

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]

[1] 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:https://dx.doi.org/10.1016/j.jmb.2019.04.002

[2] 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:https://dx.doi.org/10.1016/j.jmb.2019.04.002

[3] 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:https://dx.doi.org/10.1016/j.jmb.2019.04.002

[4] ttps://doi.org/10.1021/cr030102i

[5] 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

[6] : https://dx.doi.org/10.2210/pdb3ZWF/pdb

[7] ttps://doi.org/10.1101/575373

[8] 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

[9] : https://dx.doi.org/10.2210/pdb3ZWF/pdb

[10] : https://dx.doi.org/10.2210/pdb3ZWF/pdb

[11] : https://dx.doi.org/10.2210/pdb3ZWF/pdb

[12] : https://dx.doi.org/10.2210/pdb3ZWF/pdb

[13] : https://dx.doi.org/10.2210/pdb3ZWF/pdb

[14] : https://dx.doi.org/10.2210/pdb3ZWF/pdb

[1] 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

[2] ttps://doi.org/10.1101/575373

[3] : https://dx.doi.org/10.1101/819797

[4] ttps://doi.org/10.1101/575373

[5] ttps://doi.org/10.1101/575373

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@@ Line 1: / Line 1: @@
-==Titin==
+=='''Beta Lactamase'''==
-<StructureSection load='1TIT' size='340' side='right' caption='Caption for this structure' scene=''>
+<StructureSection load='3ZWF' size='340' side='right' caption='tRNAse Z Metallo-Beta Lactamase (homosapien)' scene=''>
-This is a default text for your page '''Sandbox GGC5'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.
-You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.
-== Function ==
+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.
-== Disease ==
+=='''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>.
+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.
-== Relevance ==
+[[Image:beta lactam ring in antibiotics.png]]
+Beta Lactam Ring present in Antibiotics
-== Structural highlights ==
+[[Image:Penicillin inhibition.svg]]
+Penicillin inhibition
+=='''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>.
+=='''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.
+=='''Structural highlights'''==
+Macromolecules:
+Two chains (A,B) of Zinc phosphodiesterase ELAC Protein 1 <ref>DOI 10.2210/pdb3ZWF/pdb</ref>.
+''Unique Ligands''
+- 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>.
+<scene name='78/781193/2_zincs/1'>Zinc ions are adjacent to the phosphate to balance the charge</scene>
+- 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>.
+<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. Secondary structure <scene name='78/781193/Hydrophobic_structure/1'>This is a secondary view of the titin structure</scene>
 </StructureSection>
-== References ==
+=='''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>.
+== '''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.
+== '''References''' ==
 <references/>
+[1]
+[2]
+[3]
+[4]
+[5]
+[6]
+[7]
+[8]

Sandbox GGC5: Difference between revisions

Latest revision as of 19:52, 28 April 2021

Contents

Beta Lactamase

Contents

Background Information

Mechanism of Antibiotic Beta Lactam Ring Resistance

Beta Lactamase in Humans (PDB: 3ZWF)

Structural highlights

Disease

Evolutionary Considerations

References

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