Laboratory of Bioinorganic Chemistry
Graduate School of Science
Professor

Associate Professor
Assistant Professor

Yasuhiro FUNAHASHI
Masaki NOJIRI

Tsubasa HATANAKA

funahashi
nojirihatanakat13

URL: http://www.chem.sci.osaka-u.ac.jp/lab/funahashi/
In biological processes such as energy
transfer and metabolism, photoexcitation,
electron transfer, and molecular conversion
reactions are smoothly carried out. In thenarrow space of metalloproteins, which areresponsible for these reactions, there arereaction-active metallic sites, and these sites
are the center of the reactions.
Metalloproteins and artificially synthesized
metal complexes share the same propertiesof their central metal ions. Furthermore,some metal complexes exhibit
pharmacological activity in vivo. Our
research is focused on understanding therelationship between metals and life, and on
developing functional complexes and artificial
metalloenzymes that contain related metals.
Molecular activation of metal
active centers

Transition metal-containing proteins
include those involved in respiration,
photosynthesis, and associatedelectron transfer, as well as enzymes
with catalytic functions. For example,
the reduction of oxygen molecules towater at the end of the respiratory
chain by transporting and storingsmall molecules of oxygen is carriedout by a group of metalloproteins.
There are also numerous
metalloenzymes that activate oxygen
molecules to oxidize various substrates
and scavenge reactive oxygen species.
Transition metals are essential
cofactors in the active sites of these
metalloenzymes, including heme- andnon-heme iron, type II and type III
copper, and manganese. Manganeseclusters also catalyze the reaction thatgenerates oxygen from water inphotosynthesis. Zinc-containing
metalloenzymes are also used tocatalyze carbon dioxide release inrespiration and protein hydrolysis indigestion, respectively. Thus, we areinterested in the function of transition
metals in the active site of proteins,which activate oxygen, hydrogen,nitrogen, and their related compounds
and other substrate molecules.

Photoexcitation and electron transfer
In photosynthesis and respiration, the transfer
of energy necessary for biological activities firsttakes place using electrons as carriers. For
example, in the light reaction of oxygen-evolving
photosynthesis, photoexcited electrons movethrough proteins to produce NADPH. On theother hand, holes are transferred to themanganese cluster and annihilated by wateroxidation to produce oxygen. Both processes
contribute to the proton concentration gradientand also promote ATP synthesis. Intermediate
electron transfer in the Z-scheme is carried out
by a series of electron-transfer proteins
containing transition metals such as redox-active
heme iron and iron-sulfur clusters and type I
copper. These electron and proton transfer
processes depend not only on the dynamics ofthe protein structure but also on quantum
effects such as tunneling, which is the subject ofour research.

Development of Artificial
Metalloenzymes
By studying metalloproteins from the above
perspective, one of our first goals is toelucidate the correlation between function andstructure of metalloproteins. Life has actively
incorporated metals as essential elements since
the beginning of its development.The study ofproteins also leads to an understanding of theorigin of life and subsequent molecularevolution.

On the other hand, the active sites of natural
metalloproteins and artificially synthesized
metal complexes share similar chemical
properties, and some of them have acquired
the photosensitizing ability necessary for theutilization of light energy. We are also
working on the development of new functional
complexes containing metals related tometalloproteins and artificial metalloenzymes.
Synthesis of metal complexes with
anticancer activity
We are developing a metal complex as an
anticancer drug that causes apoptosis ofmetastasizing cancer cells by inhibiting theintracellular signal transduction mechanism.
We welcome energetic

people who are willing totake on challenges.

Department of Biological Sciences
Graduate School of Science, Osaka University
1-1, Machikaneyama-cho, Toyonaka, Osaka
560-0043, Japan
TEL: +81-6-6850-5767
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