= Stewart Shuman
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Stewart Shuman is a <biochemist> who investigates how <enzymes> modify and repair <nucleic acids>. His laboratory combines <biochemistry>, <structural biology> and <genetics> to connect a particular <chemical reaction> with the <protein> machinery that performs it.<Stewart Shuman laboratory profile at Sloan Kettering Institute>[Research statement and RNA ligases and RNA repair project]{ref}
With <Anupam K. Chakravarty>, Shuman tested competing <reaction mechanisms> for the <RNA ligase> <RtcB>. The question concerned the chemistry of the broken <RNA> ends: did a cyclic phosphate join directly to an opposing hydroxyl end, or did opening and activation precede sealing? Their 2012 experiments supported a <GTP>-dependent pathway involving <hydrolysis>, activated <reaction intermediates> and formation of a new <phosphodiester bond>.<GTP-dependent RtcB RNA splicing by Anupam K. Chakravarty and Stewart Shuman>[Abstract and Figure 1: alternative mechanisms; Results: GTP requirement and kinetic intermediacy]{ref}
The logical force of such an experiment can be seen without assuming that a successful final reaction reveals every step. Suppose mechanisms A and B both predict a joined <RNA> molecule, but A requires <GTP> even when the starting end already contains a cyclic phosphate, whereas B predicts that this substrate bypasses the <GTP> requirement. Comparing otherwise equivalent reactions with and without <GTP> distinguishes those predictions. Detecting an intermediate also requires attention to <chemical kinetics>: a species appearing only after product accumulation cannot explain an earlier obligatory step. These are general reasons to combine selective changes in starting chemistry with time-resolved measurements, rather than identifying a <reaction mechanism> solely from the final product.
\Image[https://www.mskcc.org/sites/default/files/styles/width_200_1x1/public/node/1531/person/shuman-stewart_200813_03-1200x800.jpg?h=10d202d3]
{title=Stewart Shuman}
{description=Portrait identified by the named Sloan Kettering Institute laboratory profile.}
{height=200}
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