Synthetic protein mimics structure, function of metalloprotein in nature

December 10, 2009
Scientists led by chemist Yi Lu have designed a synthetic protein that is both a structural model and a functional model of a native protein, nitric-oxide reductase. Photo by L. Brian Stauffer

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 "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."

Source: University of Illinois at Urbana-Champaign (news : web)

Explore further: Reducing side-effects of painkillers

Related Stories

Reducing side-effects of painkillers

September 12, 2006

Cardiff University researchers have increased the understanding of why some painkillers increase the risk of heart attack and stroke.

Nitric oxide regulates plants as well as people

April 28, 2008

Nitric oxide has emerged as an important signaling molecule in plants - as in mammals including people. In studies of a tropical medicinal herb as a model plant, researchers have found that nitric oxide targets a number of ...

Multiple axons and actions with PSD-95

December 15, 2008

Nitric oxide gets neurons together. And it seems to do it backward. Work by Nikonenko et al. suggests that a protein called PSD-95 prompts nitric oxide release from postsynaptic dendritic spines, prompting nearby presynaptic ...

Nitric oxide shown to cause colon cancer

January 20, 2009

(PhysOrg.com) -- Researchers long ago established a link between inflammation, cancer and the compound nitric oxide, which may be produced when the immune system responds to bacterial infections, including those of the colon. ...

Recommended for you

Brazilian wasp venom kills cancer cells by opening them up

September 1, 2015

The social wasp Polybia paulista protects itself against predators by producing venom known to contain a powerful cancer-fighting ingredient. A Biophysical Journal study published September 1 reveals exactly how the venom's ...

Water heals a bioplastic

September 1, 2015

A drop of water self-heals a multiphase polymer derived from the genetic code of squid ring teeth, which may someday extend the life of medical implants, fiber-optic cables and other hard to repair in place objects, according ...

Naturally-occurring protein enables slower-melting ice cream

August 31, 2015

(Phys.org)—Scientists have developed a slower-melting ice cream—consider the advantages the next time a hot summer day turns your child's cone with its dream-like mound of orange, vanilla and lemon swirls with chocolate ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

dreadnought
not rated yet Dec 12, 2009
This is a great breakthrough. If we can better understand the structure-function relationship of proteins, the better we will be able to design our own proteins.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.