User:Jason Garcia/Sandbox1

NpmA: Methlytransferase in Escherichia Coli

spinqualitylabelsall models SAM Dependent Methyltransferase NpmA= Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D This is a default text for your page Jason Garcia/Sandbox1. Click above on edit this page to modify. Be careful with the < and > signs. You may include any references to papers as in: the use of JSmol in Proteopedia or to the article describing Jmol to the rescue. Introduction Functioning as a plasmid-mediated methyltransferase, NpmA was discovered in Japan, 2003, and confers a high level of aminoglycoside antibiotic resistance against most antibiotics in-class. NpmA uses an S-adenosyl-methionine (SAM) as a methyl group cofactor to remove a methyl group from SAM, converting it to S-adenosyl-homocysteine (SAH), and add it to the 30S ribosome unit. This addition prevents the binding of aminoglycosides and blocks their ability to shut down the ribosome and RNA transcription. . Mechanism Error creating thumbnail: File with dimensions greater than 12.5 MP Figure 1: NpmA Mechanism Figure 1 depicts the proposed biochemical mechanism of action of NpmA and SAM. N1 of A1408 attacks the methyl group of SAM, converting it to SAH. The most likely candidate for an enzymatic base in the reaction is D35 based off of the crystal structure and its proximity to the reaction site. Active Site Error creating thumbnail: File missing Figure 2: NpmA Active Site Interactions RNA Stabilization Near the active site of NpmA, there are some regions that help in RNA stabilization. One of these regions involved W107 and W197 , which uses aromatic stacking with the tryptophan's' indole groups to stablize the A1408 of the RNA. Another region that assists in RNA stabilization. Disease Development of antibiotic resistance via NpmA forces the use of other antibiotics, as non-aminoglycosides are still effective in treatment. Future research could explore the possibilities of the development of an aminoglycoside to attack the 50S ribosomal subunit, a change in structure to bypass the additional blocking methyl group, the development of an NpmA "breaker" to destroy the protein, or a CRISPER-Cas9 gene attack to remove the gene that encodes for NpmA. Relevance The propagation of NpmA develops antibiotic resistance through its spread via plasmid-mediation, further highlighting itself as a target for understanding and combating antibiotic resistance. 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

W107 and W197

Student Contributors

Jason Garcia Ashton Lake Hayden Teague

Proteopedia Page Contributors and Editors (what is this?)

Jason Garcia