Literature DB >> 16302811

Binding of the anticancer prodrug CB1954 to the activating enzyme NQO2 revealed by the crystal structure of their complex.

Majed AbuKhader1, John Heap, Cristina De Matteis, Barrie Kellam, Stephen W Doughty, Nigel Minton, Massimo Paoli.   

Abstract

CB1954 is an attractive prodrug for directed-enzyme prodrug therapy (DEPT) and a conventional prodrug against tumors in which the enzyme NQO2 is highly expressed. We have determined the crystal structure of the NQO2-CB1954 complex to 2.0 A resolution. The binding of the prodrug is governed by hydrophobic forces, while two key electrostatic contacts determine the specific orientation of the ligand. The structure also reveals an unfavorable interaction, therefore suggesting possible avenues for DEPT-tailored engineering studies.

Entities:  

Mesh：

Substances：

Year:  2005        PMID： 16302811     DOI： 10.1021/jm050730n

Source DB:  PubMed          Journal:  J Med Chem        ISSN： 0022-2623            Impact factor:   7.446


  11 in total

1.  Crystallization and preliminary X-ray characterization of the Bacillus amyloliquefaciens YwrO enzyme.

Authors:  Majed M AbuKhader; John Heap; Cristina I De Matteis; Stephen W Doughty; Nigel Minton; Max Paoli
Journal:  Acta Crystallogr Sect F Struct Biol Cryst Commun       Date:  2007-08-10

2.  Design, synthesis, and biological evaluation of potent quinoline and pyrroloquinoline ammosamide analogues as inhibitors of quinone reductase 2.

Authors:  P V Narasimha Reddy; Katherine C Jensen; Andrew D Mesecar; Phillip E Fanwick; Mark Cushman
Journal:  J Med Chem       Date:  2011-12-29       Impact factor: 7.446

3.  Interplay of flavin's redox states and protein dynamics: an insight from QM/MM simulations of dihydronicotinamide riboside quinone oxidoreductase 2.

Authors:  Robyn M Mueller; Michael A North; Chee Yang; Sanchita Hati; Sudeep Bhattacharyya
Journal:  J Phys Chem B       Date:  2011-03-16       Impact factor: 2.991

4.  X-ray structural studies of quinone reductase 2 nanomolar range inhibitors.

Authors:  Scott D Pegan; Megan Sturdy; Gilles Ferry; Philippe Delagrange; Jean A Boutin; Andrew D Mesecar
Journal:  Protein Sci       Date:  2011-05-23       Impact factor: 6.725

5.  Mechanism-based inhibition of quinone reductase 2 (NQO2): selectivity for NQO2 over NQO1 and structural basis for flavoprotein inhibition.

Authors:  Marine Dufour; Chao Yan; David Siegel; Marie A Colucci; Matthew Jenner; Neil J Oldham; Joe Gomez; Philip Reigan; Yazhuo Li; Cristina I De Matteis; David Ross; Christopher J Moody
Journal:  Chembiochem       Date:  2011-04-19       Impact factor: 3.164

6.  Evidence for NQO2-mediated reduction of the carcinogenic estrogen ortho-quinones.

Authors:  Nilesh W Gaikwad; Li Yang; Eleanor G Rogan; Ercole L Cavalieri
Journal:  Free Radic Biol Med       Date:  2008-11-01       Impact factor: 7.376

7.  Cyclic Changes in Active Site Polarization and Dynamics Drive the 'Ping-pong' Kinetics in NRH:Quinone Oxidoreductase 2: An Insight from QM/MM Simulations.

Authors:  Clorice R Reinhardt; Quin H Hu; Caitlin G Bresnahan; Sanchita Hati; Sudeep Bhattacharyya
Journal:  ACS Catal       Date:  2018-11-14       Impact factor: 13.084

8.  Kinetic, thermodynamic and X-ray structural insights into the interaction of melatonin and analogues with quinone reductase 2.

Authors:  Barbara Calamini; Bernard D Santarsiero; Jean A Boutin; Andrew D Mesecar
Journal:  Biochem J       Date:  2008-07-01       Impact factor: 3.857

Review 9.  Azoreductases in drug metabolism.

Authors:  Ali Ryan
Journal:  Br J Pharmacol       Date:  2016-09-02       Impact factor: 8.739

10.  The structure of the leukemia drug imatinib bound to human quinone reductase 2 (NQO2).

Authors:  Jonathan A Winger; Oliver Hantschel; Giulio Superti-Furga; John Kuriyan
Journal:  BMC Struct Biol       Date:  2009-02-24
View more

北京卡尤迪生物科技股份有限公司 © 2022-2023.