TY - JOUR
T1 - Contemporary mass spectrometry for the direct detection of enzyme intermediates
AU - Kelleher, Neil L.
AU - Hicks, Leslie M.
N1 - Funding Information:
The synopsis presented here was not intended to be exhaustive. Preparation of this article was supported by grants from the Packard Foundation, the Sloan Foundation, and the NIH (GM 067725). The authors are grateful to Xuemei Han and Fred McLafferty for providing Figure 2 , Shaun McLoughlin for providing Figure 3 , and Karen Anderson for providing Figure 4 . This article is dedicated in memory of Kenneth L Rinehart at the University of Illinois.
PY - 2005/10
Y1 - 2005/10
N2 - The field of enzymology has long used small-molecule mass spectrometry. However, the direct interrogation of covalent and non-covalent intermediates by large-molecule mass spectrometry of enzymes or large peptide substrates is illuminating an increasingly diverse array of chemistries used in nature. Recent advances now allow improved detection of several modifications formed at sub-stoichiometric levels on the same polypeptide, and elucidation of intermediate dynamics with low millisecond temporal resolution. Highlighting recent applications in both ribosomal and non-ribosomal biosynthesis of natural products, along with acetyl transferases, sulfonucleotide reducatases, and PEP-utilizing enzymes, the utility of small- and large-molecule mass spectrometry to reveal enzyme intermediates and illuminate mechanism is described briefly. From ever more complex mixtures, mass spectrometry continues to evolve into a key technology for a larger number of today's enzymologists.
AB - The field of enzymology has long used small-molecule mass spectrometry. However, the direct interrogation of covalent and non-covalent intermediates by large-molecule mass spectrometry of enzymes or large peptide substrates is illuminating an increasingly diverse array of chemistries used in nature. Recent advances now allow improved detection of several modifications formed at sub-stoichiometric levels on the same polypeptide, and elucidation of intermediate dynamics with low millisecond temporal resolution. Highlighting recent applications in both ribosomal and non-ribosomal biosynthesis of natural products, along with acetyl transferases, sulfonucleotide reducatases, and PEP-utilizing enzymes, the utility of small- and large-molecule mass spectrometry to reveal enzyme intermediates and illuminate mechanism is described briefly. From ever more complex mixtures, mass spectrometry continues to evolve into a key technology for a larger number of today's enzymologists.
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U2 - 10.1016/j.cbpa.2005.08.018
DO - 10.1016/j.cbpa.2005.08.018
M3 - Review article
C2 - 16129650
AN - SCOPUS:25144446674
SN - 1367-5931
VL - 9
SP - 424
EP - 430
JO - Current Opinion in Chemical Biology
JF - Current Opinion in Chemical Biology
IS - 5
ER -