The structure of endothiapepsin complexed with the gem-diol inhibitor PD-135,040 at 1.37 A.
The crystal structure of endothiapepsin complexed with the gem-diol inhibitor PD-135,040 has been anisotropically refined to a resolution of 1.37 A. The structure of this inhibitor complex is in agreement with previous structures of endothiapepsin gem-diol inhibitor complexes that have been used to develop proposed catalytic mechanisms. However, the increase in resolution over previous structures confirms the presence of a number of short hydrogen bonds within the active site that are likely to play an important role in the catalytic mechanism. The presence of low-barrier hydrogen bonds was indicated in a previous one-dimensional H NMR spectrum.
Coates
L
L
School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, England. leightonc@bigfoot.com
Erskine
P T
PT
Mall
S
S
Williams
P A
PA
Gill
R S
RS
Wood
S P
SP
Cooper
J B
JB
D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D001665:Binding Sites; D002384:Catalysis; D003460:Crystallization; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D009025:Morpholines / Q000737:chemistry* / Q000494:pharmacology*; D014961:X-Ray Diffraction
D004791:Enzyme Inhibitors; D007093:Imidazoles; D009025:Morpholines; C480723:PD-135,040; D016282:Aspartic Acid Endopeptidases; C042466:Endothia aspartic proteinase