Study of important protein part of 2001 Keck Center conference

Study of important protein part of 2001 Keck Center conference
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Membrane proteins make up more than 30 percent of the genes in sequenced genomes, but less than 1 percent of the known protein structures. Solving the structure of the membrane protein glycophorin A led to Kevin MacKenzie’s development of a model to increase that protein’s stability.

MacKenzie, assistant professor of biochemistry and cell biology at Rice, discussed his work in a talk entitled “Understanding Membrane Protein Stability and Specificity” at the W.M. Keck Center for Computational Biology 2001 annual research conference Sept. 21.

MacKenzie’s presentation was one of three at the daylong meeting held in Galveston. In addition, 52 research posters were presented.

Membrane proteins reside in the cell membrane, a bag that encompasses each cell, and perform essential functions such as energy metabolism, transport of nutrients and signal transduction (the means by which information is passed from the outside to the inside of a cell). Because of the paucity of information about this class of proteins, any general principles that can be gleaned about membrane protein structure may have considerable impact on the field, MacKenzie said.

In his research, MacKenzie determines the structures of membrane proteins with nuclear magnetic resonance spectroscopy, which uses high magnetic fields and radio frequency pulses to determine the spatial arrangement of atoms.

Using a computational model for the behavior of the protein, he designed mutations to increase the stability of glycophorin A.

“The test of a model is to see if it can suggest a new experiment and predict the result,” MacKenzie said. “Our work with glycophorin A shows that simple models that describe the shapes of protein sidechains can predict how mutations will affect interactions within cell membranes.”

MacKenzie said the present challenge is to extend these models to more complicated protein systems. His work in the Department of Biochemistry and Cell Biology at Rice focuses on membrane protein interactions involved in biological processes such as signal transduction and apoptosis, the process of programmed cell death that is invoked by cells if things go wrong, such as being infected by a virus.

Other presenters at the Keck Center conference included Glen Legge, Department of Chemistry, University of Houston, who spoke on “Activation and ICAM-1 Recognition of the Alpha-L/Beta-2 Integrin,” and Keith Baggerly, Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, and Bruce A. Luxon, director of bioinformatics, Sealy Center for Structural Biology at The University of Texas Medical Branch (UTMB) at Galveston, who gave a joint presentation called “An Overview Analysis of Micro-array Data.”

Rice graduate student Andrew Lee of the Houston Area Molecular Biophysics Program, Department of Biochemistry and Cell Biology, won an honorable mention for his poster, “Dynamic Interactions of the ‘E. Coli’ Reca Nucleoprotein Filament with Double-Stranded DNA: Rapid DNA Homology Testing During the Earliest Detectable Phases of DNA Strand Exchange.”

Poster winners included Richard Mursinna, graduate student, Department of Biology and Biochemistry, University of Houston, “Noncognate and Cognate Amino Acid Recognition and Editing by ‘E. Coli’ Leucyl-Trna Synthetase,” first place; Munia Mukherjee, postdoctoral associate, Sealy Center, UTMB–Galveston, “Design and Structural Investigations of High Affinity Miniprotein Ligands to Streptiavidin,” second place; and Scott Larson, graduate student at the Sealy Center, UTMB–Galveston, “Thermodynamic Environments in Proteins: Fundamental Determinants of Fold Specificity,” third place.

The Keck Center was established in 1990 with support from the W.M. Keck Foundation to bridge the gap between biological and computational sciences by fostering collaborations among biologists, biomedical researchers, mathematicians and computer scientists through research and training programs.

Rice University is one of the two original Keck Center institutions, along with Baylor College of Medicine. Four major public and private universities now are part of this collaborative effort, including the University of Houston, The University of Texas Health Science Center at Houston, UTMB–Galveston and The University of Texas M.D. Anderson Cancer Center.