• Tata Institute of Fundamental research, Colaba, Mumbai (400005), Maharashtra, India.
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Metalloproteins are essential for a large number of basic processes of life including photosynthesis, respiration, detoxification against toxic substances, biosynthesis of hormones etc. The biochemical function of the metal ion in a metalloprotein depends on the oxidation state, as well as on the nature of the coordinating residues and the environment around the metal ion inside the protein cavity. Understanding of the properties of the metal ion in the protein and the molecular basis of the biochemical function of the metalloprotein present fascinating challenges to chemists and form the frontier of bioinorganic chemistry, a subject at the interface of inorganic chemistry and biological sciences.

Studies of novel metal complexes as models for the metal active site in proteins by several groups all over the world have led to significant understanding of the structure and electronic properties of metalloproteins. The complexity of the protein scaffold however can not be fully achieved by the synthetic analogues, thus study the metalloproteins themselves in vitro and use of protein engineering techniques to suitably modify the active site in order to specifically identify roles of individual residues on the properties of the metal centre in the protein have become important. Recent years have seen enormous activities in this rapidly ex-panding field all over the world both for unraveling the fundamental issues such as structure and biochemical function of metalloproteins as well as for their applications as biosensors and as industrial biocatalysts.

Some of the typical Metalloenzymes/metalloproteins that has attracted our interest consist of iron (heme) or copper ion(s) at their catalytic/active centers.

They carry out several vital metabolic functions.

Oxygen transport by hemoglobin in RBC involves a Heme center.
Conversion of O2 to H2O associated with active proton pump across the mitochrondrial membrane in the Cellular respiration by


  • Identification of  the factors responsible for stabilisation of the active structure and the nature of the dynamic fluctuations in the protein cavity.
  • Understanding the mechanistic aspects of their functions.
  • Develop novel enzymes capable of catalysing reactions of molecules which otherwise are not affected by the enzyme, eg., environmental pollutants such as pesticides etc. and design functional and stable metal active sites in proteins. We have been involved in the study of structural and mechanistic aspects of the biochemical function of electron transfer and redox metalloenzymes using various physicochemical techniques such as NMR (1 & 2D), Fluorescence (both equilibrium and time-resolved),  Circular dichroism (CD), Stopped -flow kinetics, cyclic voltammetry, ESI-MS and Bioelectrochemistry of wild type, mutant proteins and their analogues with special interest on cytochrome c oxidase, cytochrome P450 and peroxidases. We are also involved in the study of interactions of surfactants and lipids with metal enzymes and their biochemical implications.


The mechanism of transmembrane electron transfer and active proton pumping by the ubiquitous respiratory enzyme, cytochrome c oxidase (CCO) is a challenging area of research in bioinorganic chemistry. We have detected redox-state dependent conformational changes in this multi-metal enzyme and has shown that there is a localized conformational change in the enzyme due the electron transfer process.  Our studies showed that the conformational changes due to electron transfer and proton translocation are complementary to each other.  Our recent studies on pH induced conformational transition in genetically engineered dicopper site of cytochrome c oxidase demonstrated the possible role of this site in the gating mechanism of the electron transfer process of the enzyme.




Biosynthesis of steroid hormones, metabolism of drugs and many xenobiotics etc., aremediated by the metalloenzyme, cytochrome P450. The mechanism of drug metabolism, substrate recognition and product selectivity by this enzyme is a frontier area of research in bioinorganic chemistry. Studies of the interaction of physiologically important substrates with different cytochrome P450 enzymes by us helped to identify subtle conformational changes near the heme active site of the enzyme. We are also involved in extensive site-specific mutagenesis of the substrate access channel as well as the substrate binding site of this important enzyme with the aim of tuning the substrate specificity and product selectivity of the enzyme.



The conformational properties and stability of the metal active center are important for the biochemical function of metal enzymes and proteins. We have determined the specific contributions of hydrogen-bonding, ionic and hydrophobic interactions on the stabilization of the active site in the plant peroxidase and showed that the high stability of the enzyme against hydrogen peroxidase arises due to extensive hydrogen bonding and salt-bridges surrounding the metal centre in the enzyme. Removal of the metal ion prosthetic group was shown to have a drastic effect on the structure of the enzyme and Our studied have also shown the existence of multiple conformational sub-states in the apoprotein of the peroxidase in solution.



Interaction of Metal proteins with surfactants and lipids: Association of various surfactants and functional lipids with the membrane bound enzyme, cytochrome c oxidase and other heme proteins has very significant role in the biochemical function and stability of these biomolecules. We have shown that while ionic surfactants deactivate and cause depletion of the metal prosthetic group from most of the metal proteins, neutral surfactants help to stabilize the active structure in them. Our work has also suggested that the cardiotoxicity of the anti-cancer drug, adriamycin possibly arises due to seggregation of the functional lipid, cardiolipins associated with the cytochrome c oxidase leading to deactivation of the enzyme. We have shown that ionic surfactants can selectively unfold the metal active site of cytochrome c and stabilize an intermediate species, which is formed in the unfolding pathway of the enzyme. These studies have elucidated a fascinating chemistry of the action of surfactants and helped in better understanding of the varying degree of structural rigidity in the metal proteins.