tailieunhanh - Báo cáo khoa học: Structural insight into the evolutionary and pharmacologic homology of glutamate carboxypeptidases II and III

Glutamate carboxypeptidase III (GCPIII) is a metalloenzyme that belongs to the transferrin receptor⁄glutamate carboxypeptidase II (GCPII; EC ) superfamily. GCPIII has been studied mainly because of its evo-lutionary relationship to GCPII, an enzyme involved in a variety of neuro-pathologies and malignancies, such as glutamatergic neurotoxicity and prostate cancer. | Structural insight into the evolutionary and pharmacologic homology of glutamate carboxypeptidases II and III Klara Hlouchova1 2 Cyril Barinka3 Jan Konvalinka1 2 and Jacek Lubkowski3 1 Gilead Sciences and IOCB Research Centre Institute of Organic Chemistry and Biochemistry Academy of Sciences of the Czech Republic Prague Czech Republic 2 Department of Biochemistry Faculty of NaturalScience Charles University Prague Czech Republic 3 Center for Cancer Research NationalCancer Institute at Frederick MD USA Keywords GCPIII M28 family metallopeptidase NAALADase II prostate specific membrane antigen Correspondence J. Lubkowski or J. Konvalinka Macromolecular Crystallography Laboratory 539 Boyles Street NationalCancer Institute at Frederick Frederick MD 21702 USA Institute of Organic Chemistry and Biochemistry Gilead Sciences IOCB Research Center Academy of Sciences of the Czech Republic Flemingovo nam. 2 166 10 Praha 6 Czech Republic Fax 301 846 7517 420 220 183 578 Tel 301 846 5494 420 220 183 218 E-mail jacek@ konval@ Database The atomic coordinates of the structures described in the present study together with the experimental structure factor amplitudes have been deposited in the RCSB Protein Data Bank with accession codes 3FF3 glutamate complex 3FEE the complex with QA 3FED the complex with EPE and 3FEC the pseudo-unli-ganded state Received 27 April2009 revised 3 June 2009 accepted 12 June 2009 doi Glutamate carboxypeptidase III GCPIII is a metalloenzyme that belongs to the transferrin receptor glutamate carboxypeptidase II GCPII EC superfamily. GCPIII has been studied mainly because of its evolutionary relationship to GCPII an enzyme involved in a variety of neuropathologies and malignancies such as glutamatergic neurotoxicity and prostate cancer. Given the potential functional and pharmacological overlap between GCPIII and GCPII studies addressing the structural and physiological properties of GCPIII