User:Jamie Abbott/Sandbox2: Difference between revisions

A comparison of <scene name='User:Jamie_Abbott/Sandbox2/Glu270_distance/1'>Glu270</scene> in the HisRS:histidinol and the HisRS:adenylate complexes provides further structural information into how Arg259 may serve a role in catalysis.  In the HisRS:histidinol complex  a water-mediated interaction exists between Glu270 and εN of Arg259.  However, in the HisRS:adenylate complex Glu270 moves to form a salt bridge with the guanidinium group excluding the water molecule.  This movement serves as a salt bridge switch that may weaken the ionic interaction between Arg259 and the α-phosphate<ref name="Arnez97" /> and stabilize adenylate formation in the active site.  Also, Arg113 as well as Arg259 are arranged to interact with <scene name='User:Jamie_Abbott/Sandbox2/His_r259_r113/3'>α-phosphate</scene> of ATP and and also stabilize negative charge developed on the non-bridging oxygens  α-phosphate during the transition state <ref name="aaRSbk" />.  Evidence for Arg259 as critical residue in catalysis is further supported by mutational studies where a two or three log decrease in activity is observed when Arg259 is substituted with histidine  <ref name="Arnez97" /> or other amino acids<ref name="arnez1">PMID: 9266856</ref>.  Utilizing Arg259 for catalysis is unique to HisRS as other class II aaRS enzymes, AspRS<ref>PMID: 7966328</ref> and SerRS<ref name="belrhali" />, use a divalent magnesium metal ion to coordinate the α-phosphate of ATP and serve as an electrophilic catalyst.