Sandbox GGC5

Beta Lactamase

spinqualitylabelsall models tRNAse Z Metallo-Beta Lactamase (homosapien) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D 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 . Some common examples of specific drugs in these classes include cefazolin, cefadroxil, penicillin, ampicillin, and methicillin . These antibiotics function by preventing bacteria from forming their cell wall, regardless if the bacteria are gram positive or gram negative . These antibiotics all contain a beta-lactam ring . 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 https://en.wikipedia.org/wiki/%CE%92-lactam_antibiotic#/media/File:Beta-lactam_antibiotics_example_1.svg File: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 . 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 . Beta Lactamase in Humans (PDB: 3ZWF) In order to make mature tRNAs, first they have to be processed . 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 . 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 . Unique Ligands - Phosphate (PO4) ligand on chains A and B of Zinc phosphodiesterase ELAC Protein 1 . - Zinc (Zn) ligand on chains A and B of Zinc phosphodiesterase ELAC Protein 1 . -1,2 Ethanediol (EDO) ligand on chains A and B of Zinc phosphodiesterase ELAC Protein 1 . - Sodium (Na+) ion on chain B of Zinc phosphodiesterase ELAC Protein 1 . Sodium ion within the protein 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.

Disease

If there are mutations in the tRNase Z metallo-beta lactamases, these enzymes have been implicated in several diseases including prostate cancer . 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 .

Evolutionary Considerations

Beta Lactamase protein structure is highly conserved across both prokaryotes and eukaryotes . Their presence indicates that these proteins are highly adaptable, with a wide range of substrates . The highly conserved nature of this structure suggests that the genetic material for beta lactamase is ancient in origin . 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

[1] [2] [3] [4] [5] [6] [7] [8]