About the Seminar:

Title:

How enzymes impart catalytic superpowers to amino acids in the active site

Abstract:

Amino acid side chains, such as the carboxylic acid groups of aspartate and glutamate, or the primary amine of lysine, are weak Brønsted acids and bases for the free amino acids in solution. How do enzyme active sites transform them into strong acids, bases, or nucleophiles? Evidence is presented that enzymes impart catalytic potency to amino acids in the active site through couplings that 1) Alter the strength of acidity/basicity and, simultaneously; 2) Expand the buffer range. To achieve an expanded buffer range, a residue must be strongly coupled either: 1) to a like-charged residues with an intrinsic pK a difference less than 1 pH unit; or 2) to an oppositely- charged residue where the intrinsic pK a of the anionic residue is higher than that of the cationic residue, with an optimal difference that is dependent on the coupling energy. Strength of acidity or basicity, as represented by shifts in pK a , are controlled by coupling to other charged residues; the expanded buffer ranges enable the correct protonation states to be populated at the operational pH. Examples are reported, showing how nearby aspartates and glutamates play significant supporting roles to catalytic aspartates and glutamates. Similarly, catalytic lysines are supported by neighboring tyrosines or cysteines, where the Tyr or Cys has the higher intrinsic pK a , or by other lysines, where the intrinsic pK a difference is less than 1 pH unit. Supported by NSF CHE-1905214, MCB-2147498 and a Fulbright Faculty Research Award.

About the Speaker:

Bio:

Dr. Mary Jo Ondrechen is an American chemist, educator, researcher, community leader and activist. She serves as Professor of Chemistry and Chemical Biology and Principal Investigator of the Computational Biology Research Group at Northeastern University in Boston, Massachusetts. Ondrechen received an American Chemical Society certified bachelor’s degree in chemistry from Reed College, Portland, Oregon. She pursued doctoral studies in Chemistry and Chemical Physics at Northwestern University, Evanston, Illinois, and earned the Ph.D. degree, under the direction of Mark A. Ratner. After postdoctoral research appointments at the University of Chicago and at Tel-Aviv University in Israel, the latter as a NATO Postdoctoral Fellow, she joined the faculty at Northeastern University in Boston, Massachusetts.

Research:

The Ondrechen Research Group (The O.R.G.) is based in the Department of Chemistry and Chemical Biology at Northeastern University in Boston, USA.

Our work spans the areas of theoretical and computational chemistry, computational biology, bioinformatics, protein design, and drug discovery.

We have collaborators in experimental chemical biology, experimental biophysics, protein engineering, medicinal chemistry, mathematics, and computer science.  Areas of interest include functional genomics – predicting the biochemical functional roles of gene products (proteins), protein engineering, providing computational guidance for drug discovery, and understanding the fundamental basis for enzyme catalysis.