Title
Ultrahigh Resolution Crystal Structures Of Human Carbonic Anhydrases I And Ii Complexed With "Two-Prong" Inhibitors Reveal The Molecular Basis Of High Affinity
Abstract
The atomic-resolution crystal structures of human carbonic anhydrases I and II complexed with "two-prong" inhibitors are reported. Each inhibitor contains a benzenesulfonamide prong and a cupric iminodiacetate (IDA-Cu 2+) prong separated by linkers of different lengths and compositions. The ionized NH- group of each benzenesulfonamide coordinates to the active site Zn2+ ion; the IDA-Cu2+ prong of the tightest-binding inhibitor, BR30, binds to H64 of CAII and H200 of CAI. This work provides the first evidence verifying the structural basis of nanomolar affinity measured for two-prong inhibitors targeting the carbonic anhydrases. © 2006 American Chemical Society.
Publication Date
3-8-2006
Publication Title
Journal of the American Chemical Society
Volume
128
Issue
9
Number of Pages
3011-3018
Document Type
Article
Personal Identifier
scopus
DOI Link
https://doi.org/10.1021/ja057257n
Copyright Status
Unknown
Socpus ID
33644956925 (Scopus)
Source API URL
https://api.elsevier.com/content/abstract/scopus_id/33644956925
STARS Citation
Jude, Kevin M.; Banerjee, Abir L.; Haldar, Manas K.; Manokaran, Sumathra; and Roy, Bidhan, "Ultrahigh Resolution Crystal Structures Of Human Carbonic Anhydrases I And Ii Complexed With "Two-Prong" Inhibitors Reveal The Molecular Basis Of High Affinity" (2006). Scopus Export 2000s. 8484.
https://stars.library.ucf.edu/scopus2000/8484