NATURE|Vol 460|13 August 2009|doi:10.1038/nature08304 REVIEW
Yi Lu1, Natasha Yeung1, Nathan Sieracki1 & Nicholas M. Marshall1
Metalloproteins account for nearly half of all proteins in nature. Protein
metal-binding sites are responsible for catalysing important biological
processes, such as photosynthesis, respiration, water oxidation, molecular
oxygen reduction and nitrogen fixation. Much effort has been devoted
to understanding the structure and function of metalloproteins, as summarized
by other reviews in this Insight. The ultimate test is to use this
knowledge to design new metalloproteins that reproduce the structures
and functions of native metalloproteins1–3. Metalloprotein design is not
just an intellectual exercise that duplicates biochemical and biophysical
studies of native metalloproteins. This ‘bottom-up’ approach can also elucidate
structural features that may remain hidden in those studies. Whereas
biochemical and biophysical studies mostly reveal individual features that
result in a loss of function, design requires the incorporation of all the
structural features needed to attain a function. Equipped with insights
from design processes, it may be possible to design new metalloproteins
with improved properties such as higher stability and greater efficiency,
or to impart them with functions not found in nature, for use in an even
wider range of biotechnological and pharmaceutical applications.