Sandbox GGC5

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==FABP3 with myristic acid==
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=='''Beta Lactamase'''==
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<StructureSection load='78/781193/Overall/1'</scene>
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<StructureSection load='3ZWF' size='340' side='right' caption='tRNAse Z Metallo-Beta Lactamase (homosapien)' scene=''>
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Heart-type Fatty acid-binding proteins (H-FABP/FABP3) are cytoplasmic carrier protein that active fatty acid metabolism in the heart; found in cardiomyocytes.
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== Function ==
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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.
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Heart-type fatty acid binding protein (H-FABP) found in heart and skeletal muscle tissue. FABP3 involved in fatty acid metabolism by myristic acid.
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Myristic acid is long saturated fatty acid chain that found in plant and animal, especially in milk fat. It produced during human metabolism and binds with FAPB3.
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Hexaethylene glycol used in crystallized FABP3 with myristic acid.
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== Disease ==
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=='''Background Information'''==
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Pulmonary Embolism is lung disease that occurs when blood clots block the one of the pulmonary arteries. It blocks blood and oxygen flow and can causes pulmonary infarction when it gets severe. <br />
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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>.
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Acute Myocardial Infarction is heart attack that due to cholesterol, saturated fat, and trans-fat build plaque and block the arteries which causes cardio tissue damage.
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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.
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[[Image:beta lactam ring in antibiotics.png]]
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Beta Lactam Ring present in Antibiotics
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[[Image:Penicillin inhibition.svg]]
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Penicillin inhibition
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=='''Mechanism of Antibiotic Beta Lactam Ring Resistance'''==
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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>.
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=='''Beta Lactamase in Humans (PDB: 3ZWF)'''==
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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.
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=='''Structural highlights'''==
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Macromolecules:
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Two chains (A,B) of Zinc phosphodiesterase ELAC Protein 1 <ref>DOI 10.2210/pdb3ZWF/pdb</ref>.
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''Unique Ligands''
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- Phosphate (PO4) ligand on chains A and B of Zinc phosphodiesterase ELAC Protein 1 <ref>DOI 10.2210/pdb3ZWF/pdb</ref>.
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<scene name='78/781193/Po4/1'>PO4 Ligand</scene>
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- Zinc (Zn) ligand on chains A and B of Zinc phosphodiesterase ELAC Protein 1 <ref>DOI 10.2210/pdb3ZWF/pdb</ref>.
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<scene name='78/781193/2_zincs/1'>Zinc ions are adjacent to the phosphate to balance the charge</scene>
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- 2007 hydrophobic amino acid residues <ref>DOI 10.2210/pdb3ZWF/pdb</ref>.
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<scene name='78/781193/Hydrophobic_amino_acids/1'>hydrophobic amino acid properties </scene>
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- 1878 polar amino acid residues <ref>DOI 10.2210/pdb3ZWF/pdb</ref>.
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<scene name='78/781193/Polar_amino_acids/1'>polar amino acids</scene>
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- Sodium (Na+) ion on chain B of Zinc phosphodiesterase ELAC Protein 1 <ref>DOI 10.2210/pdb3ZWF/pdb</ref>.
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<scene name='78/781193/Sodium_ion_enlarged/1'>Sodium Ion present</scene>
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== Structure ==
 
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<scene name='78/781193/Overall/1'>4 amino acids</scene> Lysine (orange), arginine (turquoise), tyrosine (purple), and serine (yellow) <br />
 
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<scene name='78/781193/Myr_hydrogen_bonds/2'>Myristic acid</scene> Tyr128 formed hydrogen bond with O2 of MYR and epsilon nitrogen and one of NH2 of Arg128 formed hydrogen bond with hydroxyl MYR. <br />
 
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<scene name='78/781193/P6g_with_lys_and_ser/2'>Hexaethylene glycol</scene> Lys37 formed hydrogen bond with 4 oxygens (1,4,7, and 10) of P6G and ketone group of Ser34 formed hydrogen bond with hydroxyl group of P6G.
 
</StructureSection>
</StructureSection>
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=='''Disease'''==
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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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== '''Evolutionary Considerations''' ==
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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.
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== '''References''' ==
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<references/>
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== References ==
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[1]
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<references/Matsuoka, Shigeru, et al. “Water-Mediated Recognition of Simple Alkyl Chains by Heart-Type Fatty-Acid-Binding Protein.” Angewandte Chemie International Edition, vol. 54, no. 5, 2014, pp. 1508–1511., doi:10.1002/anie.201409830.>
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[2]
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<references/Myristic acid and Lauric acid. https://www.acs.org/content/acs/en/molecule-of-the-week/archive/m/myristic-acid.html (accessed Nov 6, 2019).>
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[3]
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<references/National Center for Biotechnology Information. PubChem Database. Myristic acid, CID=11005, https://pubchem.ncbi.nlm.nih.gov/compound/Myristic-acid (accessed on Nov. 6, 2019)>
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[4]
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<references/Mechanic, O. J. (2019, August 15). Acute Myocardial Infarction. Retrieved from
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[5]
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https://www.ncbi.nlm.nih.gov/books/NBK459269/.>
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[6]
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<references/Pulmonary embolism. (2018, March 7). Retrieved from https://www.mayoclinic.org/diseases
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[7]
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conditions/pulmonary-embolism/symptoms-causes/syc-20354647.>
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[8]

Current revision

Contents

Beta Lactamase

tRNAse Z Metallo-Beta Lactamase (homosapien)

Drag the structure with the mouse to rotate

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

  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:http://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:http://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:http://dx.doi.org/10.1016/j.jmb.2019.04.002
  4. ↑ https://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:http://dx.doi.org/10.1080/10409230701279118
  6. ↑ doi: https://dx.doi.org/10.2210/pdb3ZWF/pdb
  7. ↑ https://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:http://dx.doi.org/10.1080/10409230701279118
  9. ↑ doi: https://dx.doi.org/10.2210/pdb3ZWF/pdb
  10. ↑ doi: https://dx.doi.org/10.2210/pdb3ZWF/pdb
  11. ↑ doi: https://dx.doi.org/10.2210/pdb3ZWF/pdb
  12. ↑ doi: https://dx.doi.org/10.2210/pdb3ZWF/pdb
  13. ↑ doi: https://dx.doi.org/10.2210/pdb3ZWF/pdb
  14. ↑ doi: https://dx.doi.org/10.2210/pdb3ZWF/pdb
  15. ↑ 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
  16. ↑ https://doi.org/10.1101/575373
  17. ↑ doi: https://dx.doi.org/https
  18. ↑ https://doi.org/10.1101/575373
  19. ↑ https://doi.org/10.1101/575373

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