Michael Witty

          This page is under construction. While much of the information is still relevant, I plan to update this site in 2012 to include the American Chapter of my amazing life. In the meantime you could look at my poll - scroll to the bottom of this page!

          Now I work in Marine Microbiology, but short descriptions of my previous research will illustrate the knowledge and experience I can bring to teaching and research projects. My Post-doctoral work from 1996 to 2002 involved contributions to two projects within diverse and multidisciplinary groups. They are engaged in research into the structural biology and post translational processing of bacterial proteins.

Tol protein crystals

          Tol proteins are receptors at or near the surface of the pathogen Pseudomonas aeruginosa. My work with the TolA III protein has shown me that many crystal forms can be seen for one protein. I interpret this example as different views of the same crystal form and different rates of growth from various crystal faces and sub-faces during the growth process.

The Tol protein

          In Gram-negative bacteria, two membranes separate the cytoplasm and the outside world. The outer membrane contains pore-like proteins that allow passage of small molecules. The inner membrane has proteins that stretch across the periplasmic space and allow the energy-dependent uptake of nutrient molecules and the assembly of surface structures, such as pili. The cellular envelope is maintained in part by translation of the tol-pal operons. Mutations in the tol genes cause tolerance to colicins and filamentous phage infection. Proteins encoded by these adjacent operons include TolA, TolQ and TolR, which form a complex in the inner membrane, whose natural role is unknown. The Pseudomonas Group works on the three way interaction of filamentous bacteriophage, pili and membrane bound receptor protein: TolA. I have obtained structural data for the Pseudomonas aeruginosa TolA protein and heavy metal derivatives (Witty et al 2002). This was achieved by peptide mapping to define Tol domain structure and crystallisation of domain III with additional work on SAX analysis of domain II.

My animation of the TolA III domain, (Witty et al 2002).

The Pan pathway

          L�aspartate-a-decarboxylase (ADC) is an enzyme of the Pantothenate Biosynthesis Pathway of Escherichia�coli. ADC forms b-alanine from L-aspartate. This is a step in the pathway to pantothenate, the precursor of phosphopantetheine, the acyl carrier found in coenzyme A and in acyl carrier protein. ADC is a pyruvoyl-dependent decarboxylase with a similar mechanism to S-adenosylmethionine decarboxylase, phosphatidylserine decarboxylase, and histidine decarboxylase but no structural similarity.

          The Pan group strategy involves overproduction of all enzymes in this short (four enzyme) pathway and their mutant, processing deficient forms. ADC undergoes autocatalytic processing and I was also able to trap and purify several protein processing intermediates in sufficient quantities for crystallisation. I was involved with purification of wild type and site directed mutant forms of ADC for crystallisation. The Pan group has also recently solved the structure for Ketopantoate hydroxymethyl-transferase, a recalcitrant structure because of its large unit cell.

          Detailed knowledge of the E. coli enzymes of pantothenate biosynthesis may lead to the discovery and use of the corresponding pathogen enzymes as targets for antibiotics or plant enzymes as targets for novel herbicides. My aim is to do similar research in the future and contribute to structural and mechanistic studies. This will produce high quality data for basic science and for biotechnologies such as drug/herbicide design.

          A long standing research interest is the plant receptor-binding protein, thaumatin. My aim is to increase knowledge of plant protein secretion and maturation with this model. My long term aim is to establish my own TMP biotechnology. Thaumatin can be used as a food protein and also as a tool for the study of flavor and human taste perception.

Further information can be found at:

• Publications
• Brief curriculum vitae
• Useful (to me) links
• Briefcase cf Google Docs, cf Zoho.

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