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3-D map of enzyme could lead to more effective drugs

Date:
May 13, 2014
Source:
University of Missouri-Columbia
Summary:
A 3-D map of an enzyme called Proline utilization A (PutA) has been completed by researchers. PutA facilitates metabolism by adding oxygen to molecules. The lead investigator says that mapping this enzyme will give researchers a better understanding of its function, which could help drug manufacturers create more effective drugs.

John Tanner demonstrates how researchers in Missouri can remotely operate a powerful X-ray machine located in California, called the beamline.
Credit: Kyle Spradley

The human body is full of proteins called enzymes that help nearly every function in the body. Scientists have been studying enzymes for decades in order to learn how they work and how to create better drugs and medical treatments for many ailments. Now, University of Missouri researchers have completed a 3-D map of an enzyme called Proline utilization A (PutA). PutA facilitates metabolism by adding oxygen to molecules. John Tanner, a professor in the MU Department of Biochemistry, says mapping this enzyme will give researchers a better understanding of its function, which could help drug manufacturers create more effective drugs.

"PutA is actually two enzymes fused together to make its processing more efficient," Tanner said. "Now that we have an understanding about how PutA is constructed, we can study exactly how it works. Some dangerous bacteria, such as h. pylori, which infect stomach tissue, utilize the PutA enzyme to grow. Discovering the structure of this enzyme will provide valuable insight into how this protein functions and could provide blueprints for designing drugs that inhibit or increase certain protein functions, which would make those drugs more effective."

Tanner conducted his study by using a process called protein crystallography. This process involves growing microscopic crystals made of PutA enzymes. Tanner then shipped the protein crystals to Berkeley, Calif., where they were exposed to a high-powered X-ray device called a "beamline." (The University of Missouri is a founding member of the Molecular Biology Consortium (MBC), which operates the beamline in California.) The beamline device is one of only five in the world and is the size of a football field.

The beamline captures X-rays, focuses them on protein crystals, and records the beams that reflect or "diffract" off the crystals. Tanner decoded the diffraction patterns from his crystals to understand the precise arrangement of the atoms in the protein and created a 3-D "map" of the PutA enzyme.

"This entire project would not be possible without our access to the MBC beamline," Tanner said. "The X-ray device we have on campus has only a fraction of the power of the beamline, and we would not be able to complete this complex mapping project without such a high-powered X-ray device."

Tanner says the next step in his research is to explore the functions of each individual structure of the PutA enzyme to better understand how the enzyme works. The Department of Biochemistry is in the MU College of Food, Agriculture and Natural Resources and the MU School of Medicine. Tanner is also a professor in the Department of Chemistry in the MU College of Arts and Science.

Tanner's study was published in the Proceedings of the National Academies of Science.


Story Source:

The above story is based on materials provided by University of Missouri-Columbia. Note: Materials may be edited for content and length.


Journal Reference:

  1. H. Singh, B. W. Arentson, D. F. Becker, J. J. Tanner. Structures of the PutA peripheral membrane flavoenzyme reveal a dynamic substrate-channeling tunnel and the quinone-binding site. Proceedings of the National Academy of Sciences, 2014; 111 (9): 3389 DOI: 10.1073/pnas.1321621111

Cite This Page:

University of Missouri-Columbia. "3-D map of enzyme could lead to more effective drugs." ScienceDaily. ScienceDaily, 13 May 2014. <www.sciencedaily.com/releases/2014/05/140513132643.htm>.
University of Missouri-Columbia. (2014, May 13). 3-D map of enzyme could lead to more effective drugs. ScienceDaily. Retrieved July 23, 2014 from www.sciencedaily.com/releases/2014/05/140513132643.htm
University of Missouri-Columbia. "3-D map of enzyme could lead to more effective drugs." ScienceDaily. www.sciencedaily.com/releases/2014/05/140513132643.htm (accessed July 23, 2014).

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