Int J Biochem Mol Biol 2011;2(1):67-77
Original Article
Structural analysis of NADPH depleted bovine liver catalase and its inhibitor complexes
Ragumani Sugadev, M.N.Ponnuswamy, K. Sekar
Bioinformatics Centre, Defense Institute of Physiology and Allied Science, Lucknow Road, Timarupr, Delhi-110054, India; Department of
Crystallography and Biophysics University of Madras, Guindy Campus, Madras - 600 025, India. Bioinformatics Centre, Supercomputer
Education and Research Centre, Indian Institute of Science, Bangalore - 560 012, India. *Both authors contributed equally to this work.
Received November 29, 2010; accepted January 28, 2011; Epub January 29, 2011; published February 15, 2011
Abstract: To study the functional role of NADPH during mammalian catalase inhibition, the X-ray crystal structures of NADPH-depleted bovine
liver catalase and its inhibitor complexes, cyanide and azide, determined at 2.8Å resolution. From the complex structures it is observed that
subunits with and without an inhibitor/catalytic water molecule are linked by N-terminal domain swapping. Comparing mammalian- and fungal-
catalases, we speculate that NADPHdepleted mammalian catalases may function as a domain-swapped dimer of dimers, especially during
inactivation by inhibitors like cyanide and azide. We further speculate that in mammalian catalases the N-terminal hinge-loop region and α-
helix is the structural element that senses NADPH binding. Although the above arguments are speculative and need further verification, as a
whole our studies have opened up a new possibility, viz. that mammalian catalase acts as a domain-swapped dimer of dimers, especially
during inhibitor binding. To generalize this concept to the formation of the inactive state in mammalian catalases in the absence of tightly
bound NADPH molecules needs further exploration. The present study adds one more intriguing fact to the existing mysteries of mammalian
catalases. (IJBMB1011003).
Keywords: NADPH, bovine liver catalase, domain swapping
Full Text PDF
Address all correspondence to:
Dr. Ragumani Sugadev
Bioinformatics Centre
Defense Institute of Physiology and Allied Science
Lucknow Road, Timarupr,
Delhi-110054, India.
Tel: 001-91-9718966994, 001-11-23883185
E-mail: ragusugadev@yahoo.com
Original Article
Structural analysis of NADPH depleted bovine liver catalase and its inhibitor complexes
Ragumani Sugadev, M.N.Ponnuswamy, K. Sekar
Bioinformatics Centre, Defense Institute of Physiology and Allied Science, Lucknow Road, Timarupr, Delhi-110054, India; Department of
Crystallography and Biophysics University of Madras, Guindy Campus, Madras - 600 025, India. Bioinformatics Centre, Supercomputer
Education and Research Centre, Indian Institute of Science, Bangalore - 560 012, India. *Both authors contributed equally to this work.
Received November 29, 2010; accepted January 28, 2011; Epub January 29, 2011; published February 15, 2011
Abstract: To study the functional role of NADPH during mammalian catalase inhibition, the X-ray crystal structures of NADPH-depleted bovine
liver catalase and its inhibitor complexes, cyanide and azide, determined at 2.8Å resolution. From the complex structures it is observed that
subunits with and without an inhibitor/catalytic water molecule are linked by N-terminal domain swapping. Comparing mammalian- and fungal-
catalases, we speculate that NADPHdepleted mammalian catalases may function as a domain-swapped dimer of dimers, especially during
inactivation by inhibitors like cyanide and azide. We further speculate that in mammalian catalases the N-terminal hinge-loop region and α-
helix is the structural element that senses NADPH binding. Although the above arguments are speculative and need further verification, as a
whole our studies have opened up a new possibility, viz. that mammalian catalase acts as a domain-swapped dimer of dimers, especially
during inhibitor binding. To generalize this concept to the formation of the inactive state in mammalian catalases in the absence of tightly
bound NADPH molecules needs further exploration. The present study adds one more intriguing fact to the existing mysteries of mammalian
catalases. (IJBMB1011003).
Keywords: NADPH, bovine liver catalase, domain swapping
Full Text PDF
Address all correspondence to:
Dr. Ragumani Sugadev
Bioinformatics Centre
Defense Institute of Physiology and Allied Science
Lucknow Road, Timarupr,
Delhi-110054, India.
Tel: 001-91-9718966994, 001-11-23883185
E-mail: ragusugadev@yahoo.com
 |  |  |  |  |  |  |