CHAMPAIGN,
Ill. – Scientists have designed a synthetic protein that is both a
structural model and a functional model of a native protein,
nitric-oxide reductase.
The designed protein
“provides an excellent model system for studying nitric-oxide
reductase, and for creating biocatalysts for biotechnological,
environmental and pharmaceutical applications,” said University of
Illinois chemistry professor Yi Lu, who directed the work.
“Through rational design, we can better understand native proteins, and
maybe make one that is more efficient, more stable or more functional,”
Lu said.
While considerable progress has been made in designing proteins that
mimic the structure of native proteins, the goal of reproducing both
the structure and the function of native proteins – especially
metal-containing proteins called metalloproteins – has been elusive.
Lu’s research group, including lead author Natasha Yeung, and
collaborators at the University of Illinois and at Brookhaven National
Laboratory, are among the first to design a protein that mimics both
the structure and the function of a metalloprotein. The researchers
described their work in the journal Nature, published online on Nov. 25.
Nitric-oxide reductase is a key enzyme in the nitrogen cycle that is
critical for life. Nitric oxide plays a key role in cell signaling and
host-pathogen responses. Therefore, study of nitric-oxide reductase is
an important step toward understanding these physiological and
pathological processes.
It has been difficult to study nitric-oxide reductase, however, as it is a membrane protein that is not water soluble.
To mimic the structure and function of nitric-oxide reductase, the
researchers began with myoglobin, a small muscle protein. Although
smaller than nitric-oxide reductase and water soluble, myoglobin can
reproduce key features of the native system. Into this scaffold protein
the researchers engineered a new iron binding site consisting of three
histidines and one glutamate.
In addition to their structural roles, the histidines and glutamate in
the active site may also provide the two protons required for nitric
oxide reduction.
“The designed protein models both the structure and the function of
nitric-oxide reductase, and offers additional insight that the active
site glutamate is required for both iron binding and reduction
activity,” Lu said. ”The designed protein also serves as an excellent
model for further mechanistic studies of nitric-oxide reductase.”
Lu is affiliated with the university’s Beckman Institute, the departments of biochemistry, bioengineering, and materials science and engineering, the Frederick Seitz Materials Research Laboratory, and the Center of Biophysics and Computational Biology.
The National Institutes of Health funded the work.
