Gallery


• Pharmaceuticals


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Pharmaceuticals


1GQR - Acetylcholinesterase complexed with Rivastigmine



The carbamyl moiety is covalently linked to the active-site serine with a leaving group being retained in the 'anionic' site. A significant movement of the active-site histidine away from its normal hydrogen-bonded partner was observed, resulting in disruption of the catalytic triad. This movement may provide an explanation for the unusually slow kinetics of reactivation.

1FPU - The Abl Tyrosine Kinase domain complexed with Gleevec



Critical to the binding of Gleevec is the adoption by the kinase of an inactive conformation, in which a centrally located 'activation loop' is not phosphorylated. The conformation of this loop is distinct from that in active protein kinases, as well as in the inactive form of the closely related Src kinases. These results suggest that compounds that exploit the distinctive inactivation mechanisms of individual protein kinases can achieve both high affinity and high specificity.

1HSG - Human Immunodeficiency Virus (HIV) Protease Complexed with Indinavir



Specific interactions between the enzyme and the inhibitor include the hydroxy group of the hydroxyaminopentane amide moiety of L-735,524 ligating to the carboxyl groups of the essential Asp-25 and Asp-25' enzymic residues and the amide oxygens of the inhibitor hydrogen bonding to the backbone amide nitrogen of Ile-50 and Ile-50' via an intervening water molecule.

3ERT - Estrogen receptor alpha ligand-binding domain in complex with 4-Hydroxytamoxifen



The binding of OHT has two distinct effects on the positioning of helix 12, each of which contributes to antagonism. Helix 12 is prevented from being positioned over the ligand-binding pocket by the OHT sidechain. In addition, the alternative packing arrangement of ligand-binding pocket residues around OHT stabilizes a conformation of the LBD that permits helix 12 to reach the static region of the AF-2 surface and mimic bound coactivator.

1RG7 - Dihydrofolate reductase complexed with Methotrexate

1HW9 - Complex of the catalytic portion of human HMG-CoA reductase with Simvastatin



The statins occupy a portion of the binding site of HMG-CoA, thus blocking access of this substrate to the active site. Near the carboxyl terminus of HMGR, several catalytically relevant residues are disordered in the enzyme-statin complexes. If these residues were not flexible, they would sterically hinder statin binding.



Last Update : June 7, 2006 | Copyright ©, 2006, The Hebrew University of Jerusalem. All Rights Reserved.