The Role of the Mobile Loop in Ligand Specificity
THE ROLE OF THE MOBILE LOOP IN LIGAND SPECIFICITY
Explore the Loop Movement and its potential role in Ligand Specificity and Allosteric Interactions.
Shown above is the loop on one subunit in the absence of ligands (wheat color with loop highlighted in yellow, When NAD binds the loop starts to close (light blue subunit with loop highlighted in bright blue. Next Malate Binds (Light green subunit with loop highlighted in bright green) to give the active ternary complex and catalysis occurs.
Shown in salmon (with the closed loop highlighted in Red) is the subunit with Citrate bound, which blocks malate and hinders NAD binding. - Note that the helix in the c terminal region of the mobile loop shows a dramatic “kink” induced by Citrate.
The slate blue is the adjacent subunit across the dimer interface
Downloadable PyMol pse file used to create the above graphic
UNDERSTANDING THE CATALYTIC MECHANISM OF MALATE DEHYDROGENASE
Shown below is the Catalytic site region of Malate Dehydrogenase illustrating the positions and roles of H220, D193, R196 and R124 in proton abstrcation from the substrate Malate (H220 & D193, which is thought to change the basicity of H220) and R124 and R196 (which are thought to provide the binding energy for Malate Binding). R130 does not appear directly involved in holding Malate in the active site and may play a role in guiding Malate or Oxaloacetate into the active site depending on direction of the reaction, or release of product after catalysis.
