Simon Allard
Simon Allard (often cited as Simon T.M. Allard) is a Madison College microbiology professor. His research at the Unversity of St Andrews and the University of Wisconsin–Madison has focused on carbohydrate processing in pathogenic bacteria.
Background[edit]
Simon Allard was born in 1965 in Pontypool United Kingdom. He received his B.Sc. from King’s College, London in 1987 and then went on to study cellular pathology and toxicology at the Royal Postgraduate Medical School in London. In 1988 he completed his M.Sc. at Barts and The London School of Medicine and Dentistry followed by a Ph.D. from the University of St Andrews in 2001.
X-ray Crystallography[edit]
The esoteric art of structural biology has added considerably to the knowledge of how many important enzymes work. In 2001, whilst at the University of St Andrews, Allard published the first paper on the structure of a dTDP-D-glucose 4,6-dehydratase (rmlB), a dehydratase enzyme, (part of the lyase class of enzymes. [1]. Further work at the University of Wisconsin-Madison, including collaboration with W. Wallace Cleland, helped elucidate the mechanism of dehydratase enzymes. Cite error: Invalid <ref> tag; invalid names, e.g. too many
Scientific contributions[edit]
Although both the structure and mechanism of dehydratase enzymes are of academic interest, it is the role of rmlB in the production of the unusual sugar dTDP-L-Rhamnose that is rather intriguing.[2][3]
The reemergence of the ‘white plague’ (Tuberculosis) over the past 30 years has led to many researchers looking for ways to combat the causative organism, Mycobacterium tuberculosis. One approach is the use of protein x-ray crystallography to determine the structures of enzymes unique to M. tuberculosis with the intention of using them as possible drug targets [4] . Allard studied and characterized the enzyme rmlB, the second enzyme involved in the production of L-Rhamnose[5] [6] , a sugar not found in humans but necessary for a fully functioning mycobacterial cell wall. The importance of this work centers around the fact that the mycobacterial cell wall consists of a mycolic acid layer tethered to peptidoglycan via the polysaccharide arabinogalactan.[7] Arbinogalactan is attached to peptidoglycan via α-l-rhamnopyranosyl-(1→3)-α-d-N-acetyglucosaminosyl-1-phosphate. This structural arrangement strongly suggests that rhamnosyl residues are essential for the growth and viability of mycobacteria. [8]. Indeed, drug targeting the enzyme rmlB in M. tuberculosis, along with the other three enzymes involved in L-rhamnose biosynthesis, is an area of considerable interest. [9] [10]
References[edit]
- ↑ Allard, STM (2001). "The crystal structure of dTDP-d-glucose 4,6-dehydratase (RmlB) from Salmonella enterica serovar typhimurium, the second enzyme in the dTDP-l-rhamnose pathway". Journal of Molecular Biology. 307 (1): 283–295. doi:10.1006/jmbi.2000.4470. Unknown parameter
|coauthors=ignored (|author=suggested) (help) - ↑ TubercuList knowledge base. "rmlB". Knowledge base of new diagnostic, therapeutic and prophylactic measures against tuberculosis. Global Health Institute. Retrieved 28 January 2013.
- ↑ Ma, Y (1997). "Determination of the pathway for rhamnose biosynthesis in mycobacteria: cloning, sequencing and expression of the Mycobacterium tuberculosis gene encoding alpha-D-glucose-1-phosphate thymidylyltransferase". Microbiology. 143 (3): 937–45. PMID 9084178. Unknown parameter
|coauthors=ignored (|author=suggested) (help) - ↑ Allard, Simon (2002). "Studies on the desosamine pathway may aid in the design of novel antibiotics". Acta Crystallographica Section A. 58 (s1): c89. doi:10.1107/S0108767302088608. Unknown parameter
|coauthors=ignored (|author=suggested) (help) - ↑ Allard, Simon (2008). "•A structural perspective on the enzymes that convert dTDP-d-glucose into dTDP-l-rhamnose". Biochemical Society Transactions. 31 (3): 532–536. doi:10.1042/BST0310532. Unknown parameter
|coauthors=ignored (|author=suggested) (help) - ↑ Allard, Simon (2002). "•Toward a Structural Understanding of the Dehydratase Mechanism". Structure. 10 (1): 81–92. doi:10.1016/S0969-2126(01)00694-3. Unknown parameter
|coauthors=ignored (|author=suggested) (help) - ↑ Ullrich; Editor, Matthias (2009). "Mycobacterial Cell Wall Arabinogalactan: A Detailed Perspective on Structure, Biosynthesis, Functions and Drug Targeting". Bacterial polysaccharides : current innovations and future trends. Norfolk, UK: Caister Academic Press. ISBN 978-1-904455-45-5. More than one of
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- ↑ Ma, Yufang (2002). "Formation of dTDP-Rhamnose Is Essential for Growth of Mycobacteria". Journal of Bacteriology. 184 (12): 3392–3395. doi:10.1128/JB.184.12.3392-3395.2002. Unknown parameter
|month=ignored (help); Unknown parameter|coauthors=ignored (|author=suggested) (help) - ↑ Ma, Y (2001). "Drug Targeting Mycobacterium tuberculosis Cell Wall Synthesis: Genetics of dTDP-Rhamnose Synthetic Enzymes and Development of a Microtiter Plate-Based Screen for Inhibitors of Conversion of dTDP-Glucose to dTDP-Rhamnose". Antimicrobial Agents and Chemotherapy. 45 (5): 1407–1416. doi:10.1128/AAC.45.5.1407-1416.2001 Check
|doi=value (help). Unknown parameter|coauthors=ignored (|author=suggested) (help); zero width space character in|doi=at position 9 (help) - ↑ Babaoglu, K (2003). "Novel inhibitors of an emerging target in Mycobacterium tuberculosis; substituted thiazolidinones as inhibitors of dTDP-rhamnose synthesis". Bioorg Med Chem Lett. 13 (19): 3227–30. PMID 12951098. Unknown parameter
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