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Krishna M.G. Mallela, Ph.D.
Assistant Professor of Biophysical Chemistry
School of Pharmacy
Department of Pharmaceutical Sciences
University of Colorado at Denver and Health Sciences Center
Campus Box C238
4200 East Ninth Avenue
Denver, Colorado 80262
Office Phone: 303-315-7226
Fax: 303-315-0274
Krishna.Mallela@uchsc.edu
EDUCATION
Research Interests
Research in Dr. Mallela's laboratory focuses on understanding
the fundamental mechanisms of protein folding, stability and misfolding,
and their applications to pharmaceutical sciences and human disease
control. Detailed structural information from his previous work
using hydrogen exchange and related experiments indicated the
following three physical principles underlying protein folding
pathways. (1) Proteins are made up of small cooperative unfolding/folding
submolecular units known as foldons. (2) Proteins construct these
foldon pieces to progressively build their final native states
using the sequential stabilization principle where prior structure
guides and templates the subsequent foldons. (3) Optional misfolding
errors, which are ubiquitous, can corrupt different naturally
occurring on-pathway intermediates and cause intermediates to
accumulate by inserting error-repair barriers at different points
along the pathway. The first two principles dictate that the folding
pathway of a protein is predetermined by its component foldon
substructure, and the order of steps is set by the way the foldon
units are organized in the native structure. The third principle
determines whether the pathway appears to be kinetically 2-state
or multi-state or heterogeneous. Preliminary evidence shows that
proteins may use the same foldons to control their function. For
example, in the case of Cytochrome c, the process that triggers
the intracellular apoptotic pathway is the unfolding of its least
stable or most flexible foldon.
Selected Publications
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Krishna, M.M.G., Maity, H., Rumbley, J.N., and Englander, S.W.
(2007) "Branching in the sequential folding pathway of
cytochrome c" Protein Science, In Press.
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Krishna, M.M.G. and Englander, S. W. (2007) "A unified
mechanism for protein folding: Predetermined pathways with optional
errors" Protein Science, 16: 449-464.
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Krishna, M.M.G., Maity, H., Rumbley, J.N., Lin, Y., and Englander,
S.W. (2006) "Order of steps in the cytochrome c folding
pathway: Evidence for a sequential stabilization mechanism"
Journal of Molecular Biology, 359: 1410-1419.
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Maity, H., Maity, M., Krishna, M.M.G., Mayne. L., and Englander,
S.W. (2005) "Protein folding: The stepwise assembly of
foldon units" Proceedings of the National Academy of Sciences
of the United States of America, 102: 4741-4746.
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Krishna, M.M.G. and Englander, S.W. (2005) "The N-terminal
to C-terminal motif in protein folding and function" Proceedings
of the National Academy of Sciences of the United States of
America, 102: 1053-1058.
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Krishna, M.M.G., Lin, Y., and Englander, S.W. (2004) "Protein
misfolding: Optional barriers, misfolded intermediates, and
pathway heterogeneity" Journal of Molecular Biology, 343:
1095-1109.
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Krishna, M.M.G., Hoang, L., Lin, Y. and Englander, S.W. (2004)
"Hydrogen exchange methods to study protein folding"
Methods, 34: 51-64.
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Krishna, M.M.G., Lin, Y., Mayne, L., and Englander, S.W. (2003)
"Intimate view of a kinetic protein folding intermediate:
Residue-resolved structure, interactions, stability, folding
and unfolding rates, homogeneity" Journal of Molecular
Biology, 334: 501-513.
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Hoang, L., Maity, H., Krishna, M.M.G., Lin, Y., and Englander,
S.W. (2003) "Folding units govern the cytochrome c alkaline
transition" Journal of Molecular Biology, 331: 37-43.
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Krishna, M.M.G., Lin, Y., Rumbley, J., and Englander, S.W.
(2003) "Cooperative omega loops in cytochrome c: Role in
folding and function" Journal of Molecular Biology, 331:
29-36.
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