Revealing a pollutant's Achilles' heal

Jun 08, 2012
Figure 1: The structure of G. stearothermophilus qNOR, with the transmembrane portion visible between the brown lines. Reproduced from Ref. 1 © 2012 Yushi Matsumoto et al.

Nitric oxide (NO) is a versatile free radical that plays central roles in the environment as well as living organisms. At low concentration in the human body, for example, NO protects organs against pathogens by acting as a chemical weapon. Bacteria counter this response with respiratory enzymes called nitric oxide reductases (NORs) that effectively neutralize NO. By solving the crystal structure of the quinol-dependent reductase (qNOR) from the bacterium Geobacillus stearothermophilus (Fig. 1), a research team in Japan led by Yoshitsugu Shiro from the RIKEN SPring-8 Center, Harima, has provided insight into this microbial denitrification process.

In previous investigations of reductases, biologists had limited their focus to the enzyme called cytochrome c-dependent NOR (cNOR), despite the greater abundance of qNOR in macro-organisms. This is because cNOR exhibits similar and metal to other respiratory enzymes known as cytochrome oxidases.

To elucidate the of these respiratory enzymes, and to understand how this evolution affects , Shiro and his team compared the newly determined three-dimensional structure of qNOR to those of cNOR and the cytochrome oxidases. They discovered that the overall structures of the reductases were identical and the portions of qNOR and cNOR that span cell membranes matched those of the oxidases. However, qNOR lacked the iron-containing functional group, heme c, which provides electrons to cNOR. Unexpectedly, this domain maintained an analogous folding pattern to that of cNOR, thanks to bulky residues that compensate for the void created by the absence of heme c.  

By identifying key structural components of qNOR, Shiro and colleagues revealed the mechanism of this enzyme: the electron-donating quinol molecule interacts with the transmembrane portion of qNOR through hydrogen bonds, facilitating electron transfer to it. In addition, the crystallographic data showed that this transmembrane domain enclosed water molecules that formed a hydrophilic channel extending to the cytoplasm. Computer-aided simulations indicated that this channel could transport catalytic protons to the reaction center where NO reduction takes place. “The water channel of qNOR is located in the same region as the proton channel of oxidases—[this helps explain] how respiratory enzymes acquired their proton-pumping ability,” adds Shiro. 

The researchers are currently investigating compounds that can interact with qNOR and cNOR. “In the near future, we plan to characterize the structure and function of bacterial NOR–inhibitor complexes,” says Shiro. These inhibitors could be harnessed to reduce global nitrous oxide emissions or used in antibacterial drug design.

Explore further: Penicillin redux: Rearming proven warriors for the 21st century

More information: Matsumoto, Y., et al. Crystal structure of quinol-dependent nitric oxide reductase from Geobacillus stearothermophilus. Nature Structural & Molecular Biology 19, 238–245 (2012). 

add to favorites email to friend print save as pdf

Related Stories

Cell respiration process is identified

Apr 06, 2006

University of Helsinki scientists have identified an internal electron transfer reaction that starts the proton pump mechanism of the respiratory enzyme.

Deciphering the mechanism of an ion pump

Dec 16, 2011

From an analysis of the sodium-transporting vacuolar ATPases (V-ATPases) of the bacterium Enterococcus hirae, Takeshi Murata of the RIKEN Systems and Structural Biology Center, Yokohama, and colleagues recently ...

Recommended for you

Researchers show fruit flies have latent bioluminescence

Apr 10, 2014

New research from Stephen C. Miller, PhD, associate professor of biochemistry and molecular pharmacology, shows that fruit flies are secretly harboring the biochemistry needed to glow in the dark—otherwise ...

User comments : 0

More news stories

Chemists achieve molecular first

(Phys.org) —Chemists from Trinity College Dublin have achieved a long-pursued molecular first by interlocking three molecules through a single point. Developing interlocked molecules is one of the greatest ...

Metals go from strength to strength

To the human hand, metal feels hard, but at the nanoscale it is surprisingly malleable. Push a lump of metal with brute force through a right-angle mould or die, and while it might look much the same to the ...

Low Vitamin D may not be a culprit in menopause symptoms

A new study from the Women's Health Initiative (WHI) shows no significant connection between vitamin D levels and menopause symptoms. The study was published online today in Menopause, the journal of The North American Menopa ...

Astronomers: 'Tilt-a-worlds' could harbor life

A fluctuating tilt in a planet's orbit does not preclude the possibility of life, according to new research by astronomers at the University of Washington, Utah's Weber State University and NASA. In fact, ...