Frank Jordan

Rutgers Board of Governors Professor

office: 973-353-5470
lab: 973-353-5039

Research Interests

Research in our laboratories focuses on the structure, regulation, mechanism of action, and folding of two groups of enzymes. Our research on thiamin diphosphate (the vitamin B1 coenzyme)-dependent enzymes has followed a dual approach. Part of our group is studying how a-keto acid decarboxylascs work, including both nonoxidative and oxidative functions. Questions being asked include determining the 3-D struc-ture of the protein, the conformation and activation of the coenzymes in catalysis, the nature of proton transfer events in catalysis, and the mechanism of electron and group transfer in the oxidative processes. Tools used in these studies include high resolution X-ray crystallography (pyruvate decarboxylase, the simplest of these enzymes was solved to a resolution of 2.3A), nuclear magnetic resonance spectroscopy, molecular genetics to change amino acids in the structure to establish structure-function relationships, steady-state and pre-steady-state kinetics, and immunochemical methods. Our enzyme studies are being complemented with model organic chemical studies, in which the elementary steps of the multi-step enzymatic reactions are being modeled. From such chemical models, one can learn which step and by how much the enzyme must accelerate.

Our research on serine proteases has two principal aims. First, we are attempting to define the active center electronic structure in the enzymes in the absence and in the presence of both synthetic and protein protease inhibitors. From these studies, a picture is emerging that can differentiate ground-state vs. transition-state vs. acyl-enzyme type inhibitors, providing a convenient tool for drug design. The second part of our research focuses on the varied roles of the pro-sequence in enzymes expressed as pre-pro-proteins. Subtilisin, an alkaline bacterial protease, is the model being used (27.5 kDa), since its pro-sequence (8.5 kDa, 77 amino acids) has been shown to be important both for folding of the mature sequence, as well as for inhibiting it.

For more detail, please see the Jordan Group Web Page.