Eli Lilly Award in Biological Chemistry

Professor Minkui Luo, Memorial Sloan Kettering Cancer Center

For outstanding research in biological chemistry of unusual merit and independence of thought and originality.


Professor Minkui Luo is the recipient of the 2015 Eli Lilly Award in Biological Chemistry, in recognition of his contributions to implement chemical tools to study biologically relevant enzymes. His work has focused on functional annotation and pharmacological perturbation of protein methyltransferases (PMTs). Epigenetic regulation is essential for the development and lifespan of eukaryotic organisms. Its dysregulation has been implicated in many abnormalities including neurological disorders and cancer. Among the key players in epigenetic regulation are 10-100 PMTs across eukaryotic species. Defining the targets of PMTs is challenging, but is essential to elucidate their roles in normal physiology and disease states. Many human PMTs have also emerged as drug targets. However, pharmacological perturbation of PMTs requires high-quality chemical probes, which are still limited because of the challenge to inhibit PMTs for both potency and selectivity. These situations intrigued Professor Luo to advance two ambitious projects: (1) developing the novel Bioorthogonal Profiling of Protein Methylation (BPPM) technology to profile proteome-wide/genome-wide methylation events of designated PMTs; (2) leveraging unconventional strategies to access PMT inhibitors within the scope of PMT perturbation in general and disease therapy in particular. With the aid of the BPPM technology, the Luo lab enables uncovering hundreds to thousands of novel substrates of 80% human PMTs and defining methylation events relevant for particular biological settings or disease. The Luo lab has also formulate the platform to develop systematically PMT inhibitors of high quality by targeting distinct conformations or Cys residues of otherwise closely-related PMTs.

Pfizer Award in Enzyme Chemistry

Professor Douglas Mitchell, University of Illinois, Urbana-Champaign.

For outstanding work in enzyme chemistry where the presence of enzyme action is unequivocally demonstrated.


Professor Douglas Mitchell is the recipient of the 2015 Pfizer Award in Enzyme Chemistry. The Mitchell laboratory has a long-standing interest in the biosynthetic construction, structure, and mechanism of action of complex molecules. Our interest in this area derives from the fact that most of today’s medicines can trace their origins to natural products. Not only do architecturally complex “small” molecules from nature provide challenging targets for synthetic chemists, sometimes even inspiring the development of new reaction methodologies, the study of the naturally occurring route often uncovers novel biosynthetic enzymology. Indeed, the study of natural products continues to stimulate significant advances at the chemistry-biology-medicine interface.

One focus of our group has been to characterize a class of ribosomal peptide-derived natural products adorned with thiazole and oxazole heterocycles. The biosynthetic gene clusters for such compounds ubiquitously encode a two-domain cyclodehydratase that converts Cys and Ser/Thr residues to thiazolines and (methyl)oxazolines. Subsequently, these heterocycles sometimes undergo further processing by a FMN-dependent dehydrogenase to yield the corresponding azole heterocycle. It has long been known that the heterocycle-forming cyclodehydratase required ATP, but pinpointing the mechanism of catalysis and ATP usage presented significant unresolved challenges. The N-terminal domain (C-protein) of the cyclodehydratase is homologous to known ATP-utilizing enzymes, thus it was believed to overcome the energetically uphill reaction by coupling cyclodehydration with the hydrolysis of ATP. The C-terminal domain (D-protein) belongs to the cryptically named “YcaO” superfamily, of which there were no characterized functions. Thus, the D-protein was thought to play a regulatory or scaffolding role. Our group overturned these functional assignments by studying a heterocycle synthetase where the activities of the C- and D-proteins could be separated. The D-protein (YcaO) was found to be a catalytically competent, ATP-dependent cyclodehydratase in the absence of the C-protein. By bringing the peptide substrate in close proximity, the C-protein potentiated the activity of the D-protein by nearly 1000-fold. Using a series of isotope-labeling experiments, we determined that the D-protein utilizes ATP to directly activate the peptide backbone via a phosphorylated hemiorthoamide intermediate. Thus, the leaving group during cyclodehydration is phosphate, not water. We since have crystallized an uncharacterized YcaO protein from E. coli in collaboration with Prof. Satish Nair’s group in various nucleotide-bound and -free forms. The most conserved residues in the superfamily comprise a novel ATP-binding motif, which gratifying explained the earlier inability to bioinformatically identify this site. Our results strongly support a model where ATP utilization is a universal feature of all YcaOs, which sheds light on the probable enzymatic functions of many thousands of additional uncharacterized proteins. A minor fraction of these are expected to be involved in synthesizing heterocycles on ribosomal peptide scaffolds; the majority is expected to use ATP for novel biochemical reactions that require amide backbone activation.

The Repligen Award in Chemistry of Biological Processes

Professor John S. Blanchard, Albert Einstein College of Medicine

For outstanding contributions to the understanding of biological processes with particular emphasis on structure, function and mechanism.


Professor John S. Blanchard is the recipient of the 2015 Repligen Award in Chemistry of Biological Processes in recognition of his contributions to enzyme mechanisms and antibiotic drug resistance. His laboratory uses a combination of kinetic, isotopic and structural approaches to identify how essential enzymes in bacterial pathogens function and can be inhibited. His early efforts focused on a class of flavoenzymes responsible for maintenance of redox balance, including trypanathione reductase and mycothione reductase from the human pathogens, Trypanosoma cruzi and Mycobacterium tuberculosis. He has studied biosynthetic pathways in TB involved in L-lysine, pantothenate, branched chain amino acid and mycothiol biosynthesis. His laboratory first expressed, purified and functionally characterized the enoyl-ACP reductase from Mycobacterium tuberculosis that is the target of the first-line antitubercular compound, isoniazid. That led to his continued interest in drug resistance, including the aminoglycoside acetyltransferases that are the most clinically important of the aminoglycoside modifying enzymes. The mechanistic and structural investigations led to important insights into how regioselective acetylation could be achieved by structurally similar enzymes acting on the same substrates. He continues to study these members of the GNAT superfamily, having identified the only cAMP-dependent protein acetyltransferase from M. tuberculosis and shown how it regulates the activity of a number of enzymes involved in central carbon metabolism. His laboratory was the first to determine the structure of a pentapeptide repeat protein implicated in fluoroquinolone resistance. For the last eight years, he has worked on the blaC-encoded β-lactamase of TB, and identified inhibitors of the enzyme that restore activity to β-lactam antibiotics, including carbapenems that are active against TB. These basic studies of the enzyme are now being translated into the treatment of individuals worldwide infected with multi-drug resistant tuberculosis.

Gordon Hammes ACS Biochemistry Lectureship

Professor Frank M. Raushel, Texas A&M University

For outstanding contributions in scientific research at the interface of chemistry and biology, particularly in the realm of biochemistry, biological chemistry and molecular biology.


Professor Frank M. Raushel is the recipient of the 2015 Gordon Hammes ACS Biochemistry Lectureship in recognition of his contributions toward understanding how enzymes work. His laboratory has utilized a broad array of chemical, genetic, and structural approaches to identify the mechanistic and structural constraints that govern enzyme catalysis and substrate recognition. These efforts have lead to the elucidation of the mechanism and structure of carbamoyl phosphate synthetase, the creation of novel enzymes for the catalytic detoxification of organophosphate nerve agents, the development of a comprehensive strategy for the discovery of function for uncharacterized enzymes, and deciphering the biochemical pathway for the metabolism of phosphonates by C-P Lyase. With carbamoyl phosphate synthetase, he and his collaborators determined how this remarkable enzyme is able to marshal the assembly of carbamoyl phosphate via a reaction mechanism that requires five substrates, four sequential reactions, three distinct active sites, and two long molecular tunnels for the translocation of three unstable reaction intermediates. With phosphotriesterase he and his group developed biochemical strategies for the evolution of new enzymes with enhanced catalytic properties for the detection and destruction of the chemical warfare agents sarin, soman and VX. His group is currently focused on the development of comprehensive strategies that employ bioinformatics, computational docking, and physical library screening to decipher substrate specificities for enzymes of unknown function. These efforts have lead to the discovery of many unique enzymes including cyclic-AMP deaminase, S-adenosyl homocysteine deaminase, 8-oxoguanine deaminase, cytokinin deaminase, 6-methyl adenosine deaminase, and the entire pathway for the transformation of methyl phosphonate to methane and inorganic phosphate.

The ACS Chemical Biology Lectureship

Professor Kevan Shokat, University of California, San Francisco

For contributions that have had a major impact on scientific research in the area of Chemical Biology.


Professor Shokat is the recipient of the 2015 ACS Chemical Biology Lectureship in recognition of his work to develop chemical methods for investigating cellular signal transduction pathways—with a particular focus on protein kinases, lipid kinases, and GTPases. His lab is known for pioneering the development of a widely used chemical genetic method of pharmacologically controlling any single kinase to precisely determine the function of single members of the largest family of enzymes involved in almost all signal transduction pathways. His lab has continued to be a leader in the development of small molecules which potently and selectively alter the activity of disease causing mutated signal transduction pathways. His lab recently developed a mutant specific inhibitor of the oncogene K-Ras(G12C), which had been widely believed to be “undruggable.” His work has expanded the repertoire of small molecule regulation of protein kinases. Previously, the only pharmacological means of controlling kinase function was by way of competition for ATP resulting in kinase inhibition. His lab has expanded the pharmacological repertoire by developing “neo-substrates” of kinases, which allows activation rather than inhibition of a particular kinase, opening the door for therapy based on enhancing the protective function of stress activated kinases in Parkinson’s Disease.

The Biopolymers Murray Goodman Memorial Prize

Professor Joan A. Steitz, Yale University

For outstanding accomplishments in one or more of the areas of biochemistry, biophysical chemistry, biophysics, and/or chemical biology.

 Joan Steitz

Professor Joan A. Steitz is the recipient of the 2015 Biopolymers Murray Goodman Memorial Prize in recognition of her seminal contributions in the area of RNA structure and function. Her focus on the roles played by noncoding (nc)RNAs in the regulation of gene expression began with her postdoctoral studies, which elucidated the sequences on bacteriophage mRNA at which ribosomes bind to initiate protein synthesis. This led to her demonstration that ribosomes use complementary base pairing between the 16S rRNA and the mRNA to identify start sites. Beginning in 1979, with her MD/PhD student Michael Lerner, she identified and characterized nuclear RNA-protein complexes (snRNPs) as targets of autoantibodies from patients with Lupus. SnRNPs are the building blocks of the spliceosome that identify the ends of introns and together with many additional protein factors excise introns and ligate together exons to produce mature mRNAs. Later, her laboratory characterized other classes of snRNP particles that reside in the nucleolus (snoRNPs) or in the Cajal body (scaRNPs) and are involved in the processing and modification of ribosomal RNA precursors or of snRNAs, again by using RNA-RNA base pairing to identify their substrates. The snRNPs of the minor spliceosome, as well as the human U7 snRNP that processes the 3′-end of histone mRNAs, were discovered in her laboratory. More recent investigations of microRNAs have uncovered the coupling of their transcription and processing, as well as their upregulatory activity in quiescent cells. Concurrent studies of abundant non-coding RNAs expressed in primate cells infected by the oncogenic gamma herpesviruses EBV, KSHV and H. saimiri have recently led to functional insights that shed light on viral evolution and reveal how RNA triple-helices are used to confer stability on nuclear ncRNAs.