Research interests
Research is focussed on the structure and mechanism of action of enzymes with specific interests in enzymes of haem biosynthesis, polyketide synthases and viral and snake venom proteases.
Two polymerase enzymes are the subject of detailed investigations: porphobilinogen deaminase that assembles a tetrapyrrole in the haem biosynthesis pathway and 6-methylsalicylic acid synthase that builds the tetraketide precursor for the antibiotic patulin. These polymerase enzymes possess a molecular architecture that allows the active site to function in a specific programmed series of reactions. Using stereospecifically labelled precursors the detailed mechanism of the reaction catalysed by 6-methylsalicylic acid synthase has been investigated. Also within this polymerase theme, 5-aminolaevulinic acid dehydratase, an enzyme that catalyses the dimerisation of the haem precursor, 5-aminolaevulinic acid, is of major research interest. This zinc metalloenzyme is exceptionally sensitive to environmental lead and its inhibition leads to anaemia in human lead poisoning. Research interests extend to defining the molecular basis of human inherited diseases that affect haem synthesis enzymes in humans, including X-linked sideroblastic anaemias and porphyrias.
Other key areas of interest relate to cysteine and aspartyl proteinases and the mechanism by which they catalyse polyprotein processing in Southampton human calicivirus and human immunodeficiency virus-I (HIV-I), respectively. Interests in proteinases also include thrombin-like enzymes isolated from snake venoms and their potential as therapeutic agents. A multidisciplinary research approach is followed with organic chemists, biochemists and molecular biologists all working together in a single laboratory.
Research is underpinned by an excellent equipment base, including X-ray diffraction, high field NMR, mass spectrometry and protein/DNA synthesis and sequencing facilities.
Research group
Molecular and Cellular Biosciences