Gerald M. Alter, Ph.D.
Office: 050 Diggs Lab
Lab: 065 Diggs Lab
Ph.D.: 1975 Washington State University (J. Magnuson)
Postdoctoral: Harvard University School of Medicine (B.Vallee)
The research interests of the Alter laboratory are focused on protein/enzyme three dimensional structures, protein structural dynamics, and protein/enzyme activities, all under in vivo conditions. We are pursuing these interests by employing a combination of computational and experimental methods which will lead to an understanding of the structural basis of protein and enzyme activity. Our laboratory predicts protein structures using computational methods and tests these methods by matching predicted with observed chemical and physical properties of the proteins. These methods are well suited for determining high resolution topology of multi-protein complexes. In fact, the Nucleotide Excision Repair complex is currently under investigation using these strategies. This complex is critical for both maintaining the fidelity of genetic information stored in DNA, and as a target for cancer chemotherapies. We are also examining enzyme complexes that are critical for coordinating mitochondrial and cytoplasmic energy metabolism using the same methods. Finally, enzymes responsible for detoxifying low levels of neoteric chemical toxins and chemical warfare agents are under study.
C Zimmerle and GM Alter. Cooperativity in the mechanism of Cytoplasmic Malate Dehydrogenase. Biochemistry 32, 12743, 1993.
C Letner and GM Alter. Molecular Dynamics of Local Protein Motions in Lactate Dehydrogenase. Journal of Molecular Structure THEOCHEM 368, 205-212, 1996.
S Shaw R Geyer and GM Alter. Dissociation of Mitochondrial Malate Dehydrogenase into Active Soluble Subunits. Biochim, Biophys. Acta 1478, 248-256, 2000.
P Tung and GM Alter. Substrate and Cofactor Binding to Fluorescently Labeled Cytoplasmic Malate Dehydrogenase. Biochim Biophys. Acta, 1545, 132-145, 2001.
JM Horn, JA Lehman, GM Alter and J Gomez-Cambronero. Presence of a phospholipase D (PLD) distinct from PLD2 in human neutrophils. Biochim. Biophys Acta 1530, 97-110, 2001.
DJ Sweeney, GM Alter, ML Raymer and TE Doom. Profile Combinatorics for Fragment Selection in Comparative Protein Structure Modeling, Proceedings of the IEE International Symposium on Bioinformatics and Bioengineering, 2001.
KJ Huang, GM Alter, and DP Wooley. The Reverse Transcriptase Sequence of Human Immunodeficiency Virus Type-1 is Under Positive Evolutionary Selection Within the Central Nervous System, J. Neurovirology. 8, 281-294, 2002.
J Nuss and GM Alter. Denaturation of Replication Protein A Reveals an Alternative Conformation with Intact Domain Structure and Olignonucleotide Binding Activity. Protein Science 13, 1365-1378, 2004.
J Nuss, D Sweeney and GM Alter. Reactivity-Based Analysis of Domain Structures in Native RPA, Biochemistry 45:9804-9818 2006.