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Metrologies for Protein Structure, Function, and Modeling

Summary:

NIST researchers in the Macromolecular Structure and Function Group are involved in a joint research program with scientists from the University of Maryland Institute for Bioscience and Biotechnology Research (IBBR) that focuses on precision measurements of fundamental physical, chemical and structural properties of proteins. Together, NIST and IBBR have established world-class instrument facilities that include resources to determine protein structure using X-ray crystallography and Nuclear Magnetic Resonance (NMR). Researchers in this program are internationally recognized in the areas of computational and experimental studies of protein structure and function.

Description:

Based on its established expertise, infrastructure, and resources for structure/function studies of biological macromolecules, the program aims to impact advances in physics, chemistry, and engineering relevant to biological problems. NIST researchers also develop new technologies for application to structural studies on proteins and macromolecular complexes, for protein production, and for functional characterization of proteins. This research will have a significant contribution in systems biology since the commercialization of information and products from systems approaches will be measurement intensive.

A primary aim of this program area is to promote advanced research and interdisciplinary training in fundamental problems at the forefront of biological science through the collaboration of scientists from NIST and UMBI, with special emphasis placed on theoretical and experimental approaches to the structure and function of proteins. To meet this challenge, state-of-the-art laboratories and outstanding research groups have been established in five key areas: macromolecular structure determination by X‑ray crystallography, molecular structure and dynamics elucidation by high-field NMR, molecular biochemistry, and computational chemistry and modeling. NIST researchers and UMBI collaborators involved in this program possess significant experience and expertise in the theory and measurement of macromolecular structure-function relationships that underlie virtually all biological processes. Main areas of study include molecules and complexes of immune systems, diverse members of large enzyme families, potential drug targets in pathogenic organisms, and RNA molecules and their protein complexes. 

Recently, the approach taken by NIST and IBBR scientists in this program has been to enhance and build upon a strong foundation in the quantitative study of biomolecular systems in a way that enables a rigorous and comprehensive understanding of biological systems at a molecular level. For example, studies of a complex biological system requires the determination of the structure and function of the macromolecular components, a determination of how and when the components interact, and the ability to model the system and represent large amount of diverse data.

Major Accomplishments:

A number of protein structures have been solved from pathogenic organisms with potential applications in homeland security. These include a class IV adenylyl cyclase and chorismate mutase from Y. Pestis; a cyclic AMP receptor and a chorismate mutase from M. tuberculosis; and phzS, a pyocyanin biosynthetic protein. The high resolution structures determined for these proteins have each been deposited.

End Date:

ongoing

Lead Organizational Unit:

mml

Source of Extramural Funding:

Customers/Contributors/Collaborators:

Roy Marriuzzi, Osnat Herzberg, Scott Walsh, and John Orban (IBBR/UMBI)

Facilities/Tools Used:

The W.M. Keck Center for Structural Biology is comprised of an X-ray crystallography lab which houses a Rigaku MicroMax007 X-ray generator and two RAXIS IV++ detector equipped for cryogenic data collection and a Nuclear Magnetic Resonance (NMR) lab which houses one Bruker Biospin 500 MHz spectrometer and two Bruker Biospin 600 MHz spectrometers, one of which is equipped with a HCN triple resonance, Z-axis gradient cryoprobe system.

Staff:

Travis Gallagher
Jane Ladner
John Marino

Contact

Travis Gallagher
travis.gallagher@nist.gov
240-314-6204

Jane Ladner
jane.ladner@nist.gov
240-314-6206

John P. Marino
john.marino@nist.gov
240-314-6160