Oct. 16, 2017
Penicillin is a broad-spectrum antibacterial drug, but few of us have considered how this drug performs its primary function. Essentially, penicillin reduces the integrity of bacterial cell walls. Bacteria are constantly replenishing their cell walls when growing or reproducing much like we regenerate our skin. Expansion is accomplished via a network of enzymes and peptidoglycans, the cell wall “bricks”. Penicillin-binding proteins (PBP) belong to a subgroup of enzymes called transpeptidases and are the essential “brick-layers” for bacteria. PBPs catalyze the reaction between peptidoglycans by mediating the removal of D-alanine from the precursor of peptidoglycan. This results in a conformational change and binding of adjacent peptidoglycans. Penicillin acts as an inhibitor for this reaction. The structure of penicillin is very similar to that of the peptidoglycans, so PBP forms a bond with penicillin at the active site. In fact, it’s a covalent bond, so it’s irreversible! PBP is thence rendered inactive, peptidoglycans are left unlinked, and the bacterium’s cell wall is full of holes. Osmotic pressure builds on the bacterium as the cell wall further degrades and eventually leads to cell death. Better them than you! PBPs come in a variety. Pictured here is Penicillin-binding Protein 2a from a resistant strain of Staphylococcus Aureus strain 27r. This bacteria evolved a mutation which allows its PBP2a to resist binding to penicillin. PDB: 1VQQ
Oct. 9, 2017
With all the fresh water generated by hurricanes such as Harvey uncommon infections in the USA such as Schistosomiasis, also known as bilharzia or “snail fever” can be a worry for victims of the hurricane as well as for volunteers. The infection is a parasitic disease carried by fresh water snails infected with one of the five varieties of the parasite Schistosoma. Found predominantly in tropical and sub-tropical climates, schistosomiasis infects 240 million people in as many as 78 countries, with a vast majority of the burden occurring in Africa. Schistosomiasis ranks second only to malaria as the most common parasitic disease. Schistosomiasis is transmitted by contact with contaminated fresh water (lakes and ponds, rivers, dams) inhabited by snails carrying the parasite. Swimming, bathing, fishing can put people at risk of contracting the disease. PDBID: 5fue is the Crystal structure of Schistosoma mansoni HDAC8 complexed with 3- benzamido-benzohydroxamate
Oct. 2, 2017
New Delhi Metallo-beta-lactamase-1 (NDM-1) is an enzyme responsible for bacterial resistance to broad-spectrum antibiotics. These antibiotics share a common structure of a beta lactam ring which is susceptible to degradation by NDM-1. Misuse of antibiotics can increase drug resistance of bacteria, resulting in future infections that can become extremely difficult to treat.