Susan Miller, PhD
Professor
Pharmaceutical Chemistry
School of Pharmacy
Broadly, we use a variety of biochemical and biophysical tools to investigate protein structure/function questions spanning the range of elucidating novel aspects of catalysis in individual enzymes to understanding the interactions of proteins within a pathway and how mutations influence flux through the pathway.
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Current work is focused on understanding how key enzymes and transport proteins of bacterial mercury detoxification pathways work individually, with each other, and with other host cell proteins to rapidly remove the toxic threat of organomercurials (such as Methyl-Hg) and mercuric ions from their environment.
Awards
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- Sigma Xi, University of California, 1984
- Phi Beta Kappa, University of Missouri, 1978
- Phi Lambda Upsilon, University of Missouri, 1977
- National Merit Scholar, 1974
- Curator's Scholar Award, University of Missouri, 1974
Education & Training
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- Diversity, Equity, and Inclusion Champion Training University of California 2021
- PhD Chemistry University of California 1983
Interests
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- Enzyme mechanisms emphasizing redox systems
- protein-protein interactions
- structure-function relationships of mechanisms of regulation and catalysis
Websites
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- Bio at UCSF Department of Pharmaceutical Chemistry (pharmchem.ucsf.edu)
- Miller Lab at UCSF (smiller.ucsf.edu)
Grants and Projects
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- Bio-Organic Biomedical Mass Spectrometry Resource, NIH, 1982-2015
- Identifying Key Proteins In Hg Methylation Pathways of Desulfovibrio by Global Proteomics, DOE-Office of Science, 2011-2014
- Defining the Molecular-Cellular-Field Continuum Of Mercury Detoxification, DOE Office of Science, 2010-2014
- Molecular Mechanisms of Bacterial Mercury Transformation, DOE Office of Science, 2010-2013
- Resource for Biocomputing, Visualization, and Informatics, NIH/NCRR, 1976-2012
- Identifying Biomarkers and Mechanisms of Toxic Metal Stress with Global Proteomics, DOE-Office of Science, 2007-2011
- Function, Evolution, and Application of the Supramolecular Machines of Hg Detoxification, DOE-Office of Science, 2005-2009
- Engineering MerR for Sequestration and MerA for Reduction of Toxic Metals and Radionuclides (A. Summers, DE-FG02-99ER62865, 2002-2006
- Structure/function analysis of protein-protein interactions and role of dynamic motions in mercuric ion reductase, DOE, Office of Science, 2001-2005
- Structural Control of Hg(II) Transfer and Reduction in Mercuric Ion Reductase, NSF, 2000-2004
- Cause and Effect of Dimer Asymmetry in Mercuric Reductas, NIH, 1995-2000
Publications (45)
Top publication keywords:
Candida albicansMercuryMetals, HeavyMercury CompoundsMetallochaperonesCysteineReceptors, EstrogenBacteriaDNA Transposable ElementsLyasesKineticsBacillusMercury IsotopesOxidoreductasesFungal Proteins
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Capture of micrococcin biosynthetic intermediates reveals C-terminal processing as an obligatory step for in vivo maturation
Proc Natl Acad Sci USA 2016 Kathryn D Bewley, Philip R Bennallack, Mark A Burlingame, Richard A Robison, Joel S Griffitts, Susan M Miller -
Reconstitution and Minimization of a Micrococcin Biosynthetic Pathway in Bacillus subtilis.
Journal of bacteriology 2016 Bennallack PR, Bewley KD, Burlingame MA, Robison RA, Miller SM, Griffitts JS -
Establishing disease causality for a novel gene variant in familial dilated cardiomyopathy using a functional in-vitro assay of regulated thin filaments and human cardiac myosin.
BMC medical genetics 2015 Pan S, Sommese RF, Sallam KI, Nag S, Sutton S, Miller SM, Spudich JA, Ruppel KM, Ashley EA -
Organic and inorganic mercurials have distinct effects on cellular thiols, metal homeostasis, and Fe-binding proteins in Escherichia coli.
Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry 2015 LaVoie SP, Mapolelo DT, Cowart DM, Polacco BJ, Johnson MK, Scott RA, Miller SM, Summers AO -
X-ray structure of a Hg2+ complex of mercuric reductase (MerA) and quantum mechanical/molecular mechanical study of Hg2+ transfer between the C-terminal and buried catalytic site cysteine pairs.
Biochemistry 2014 Lian P, Guo HB, Riccardi D, Dong A, Parks JM, Xu Q, Pai EF, Miller SM, Wei DQ, Smith JC, Guo H
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Structure and dynamics of a compact state of a multidomain protein, the mercuric ion reductase.
Biophysical journal 2014 Hong L, Sharp MA, Poblete S, Biehl R, Zamponi M, Szekely N, Appavou MS, Winkler RG, Nauss RE, Johs A, Parks JM, Yi Z, Cheng X, Liang L, Ohl M, Miller SM, Richter D, Gompper G, Smith JC -
Effects of Troponin T Cardiomyopathy Mutations on the Calcium Sensitivity of the Regulated Thin Filament and the Actomyosin Cross-bridge Kinetics of Human β-Cardiac Myosin
Plos One 2013 Sommese RF, Nag S, Sutton S, Miller SM, Spudich JA, Ruppel KM -
Why Mercury Prefers Soft Ligands
J. Phys. Chem. Lett. 2013 Riccardi D, Guo H-B, Parks JM, Gu B, Summers AO, Miller SM, Liang L, Smith JC. -
Structural characterization of intramolecular Hg(2+) transfer between flexibly linked domains of mercuric ion reductase.
Journal of molecular biology 2011 Johs A, Harwood IM, Parks JM, Nauss RE, Smith JC, Liang L, Miller SM -
Discovering mercury protein modifications in whole proteomes using natural isotope distributions observed in liquid chromatography-tandem mass spectrometry.
Molecular & cellular proteomics : MCP 2011 Polacco BJ, Purvine SO, Zink EM, Lavoie SP, Lipton MS, Summers AO, Miller SM -
Drug Development Research
Evaluation of the pKa Values and Ionization Sequence of Bumetanide in Water Using 1H and 13C NMR and UV Spectroscopy 2011 Song B, Galande AK, Kodokula K, Moos WH, Miller SM -
NmerA of Tn501 mercuric ion reductase: structural modulation of the pKa values of the metal binding cysteine thiols.
Biochemistry 2010 Ledwidge R, Hong B, Dötsch V, Miller SM -
Direct measurement of mercury(II) removal from organomercurial lyase (MerB) by tryptophan fluorescence: NmerA domain of coevolved γ-proteobacterial mercuric ion reductase (MerA) is more efficient than MerA catalytic core or glutathione .
Biochemistry 2010 Hong B, Nauss R, Harwood IM, Miller SM -
Structure and conformational dynamics of the metalloregulator MerR upon binding of Hg(II).
Journal of molecular biology 2010 Guo HB, Johs A, Parks JM, Olliff L, Miller SM, Summers AO, Liang L, Smith JC -
Mechanism of Hg-C protonolysis in the organomercurial lyase MerB.
Journal of the American Chemical Society 2009 Parks JM, Guo H, Momany C, Liang L, Miller SM, Summers AO, Smith JC -
Kinetic buffering of cross talk between bacterial two-component sensors.
Journal of molecular biology 2009 Groban ES, Clarke EJ, Salis HM, Miller SM, Voigt CA -
The mechanism of inhibition of antibody-based inhibitors of membrane-type serine protease 1 (MT-SP1).
Journal of molecular biology 2007 Farady CJ, Sun J, Darragh MR, Miller SM, Craik CS -
NmerA, the metal binding domain of mercuric ion reductase, removes Hg2+ from proteins, delivers it to the catalytic core, and protects cells under glutathione-depleted conditions.
Biochemistry 2005 Ledwidge R, Patel B, Dong A, Fiedler D, Falkowski M, Zelikova J, Summers AO, Pai EF, Miller SM -
Direct monitoring of metal ion transfer between two trafficking proteins.
Journal of the American Chemical Society 2005 Ledwidge R, Soinski R, Miller SM -
Mercury adaptation among bacteria from a deep-sea hydrothermal vent.
Applied and environmental microbiology 2005 Vetriani C, Chew YS, Miller SM, Yagi J, Coombs J, Lutz RA, Barkay T -
Quantitative identification of the protonation state of histidines in vitro and in vivo.
Biochemistry 2003 Shimba N, Serber Z, Ledwidge R, Miller SM, Craik CS, Dötsch V -
Bacterial mercury resistance from atoms to ecosystems.
FEMS microbiology reviews 2003 Barkay T, Miller SM, Summers AO -
Evaluation of parameters critical to observing proteins inside living Escherichia coli by in-cell NMR spectroscopy.
Journal of the American Chemical Society 2001 Serber Z, Ledwidge R, Miller SM, Dötsch V -
High-resolution macromolecular NMR spectroscopy inside living cells.
Journal of the American Chemical Society 2001 Serber Z, Keatinge-Clay AT, Ledwidge R, Kelly AE, Miller SM, Dötsch V -
Stabilization of a novel enzyme.substrate intermediate in the Y206F mutant of Candida albicans EBP1: evidence for acid catalysis.
Biochemistry 2000 Buckman J, Miller SM -
Transient kinetics and intermediates formed during the electron transfer reaction catalyzed by Candida albicans estrogen binding protein.
Biochemistry 2000 Buckman J, Miller SM -
No metal cofactor in orotidine 5'-monophosphate decarboxylase.
Biochemical and biophysical research communications 1999 Cui W, DeWitt JG, Miller SM, Wu W -
Investigation of the kinetic mechanism of cytidine 5'-monophosphate N-acetylneuraminic acid synthetase from Haemophilus ducreyi with new insights on rate-limiting steps from product inhibition analysis.
Biochemistry 1999 Samuels NM, Gibson BW, Miller SM -
Alternative routes for entry of HgX2 into the active site of mercuric ion reductase depend on the nature of the X ligands.
Biochemistry 1999 Engst S, Miller SM -
Bacterial detoxification of Hg(II) and organomercurials.
Essays in biochemistry 1999 Miller SM -
Binding and reactivity of Candida albicans estrogen binding protein with steroid and other substrates.
Biochemistry 1998 Buckman J, Miller SM -
Rapid reduction of Hg(II) by mercuric ion reductase does not require the conserved C-terminal cysteine pair using HgBr2 as the substrate.
Biochemistry 1998 Engst S, Miller SM -
Bioorg & Med Chem Lett
Decarboxylation of 1,3- Dimethylorotic Acid Revisited: Determining the Role of N-1 1997 Wu W, Ley-han A, Wong FM, Austin TJ, Miller SM -
2'-fluoro-2'-deoxy-D-arabinoflavin: characterization of a novel flavin and its effects on the formation and stability of two-electron-reduced mercuric ion reductase.
Biochemistry 1995 Miller SM -
Drug Dev Res
Comparison of the Proteolytic Susceptabilities of Homologous L-Amino Acid, D-Amino Acid, and NSubstituted Glycine Peptide and Peptoid Oligomers 1995 Miller SM, Simon RJ, Ng S, Zuckermann, RN, Kerr JM, Moos WH -
Mechanism of p-hydroxyphenylacetate-3-hydroxylase. A two-protein enzyme.
The Journal of biological chemistry 1994 Arunachalam U, Massey V, Miller SM -
Bioorg & Med Chem Letters
Proteolytic Studies of Homologous Peptide and N-Substituted Glycine Peptoid Oligomers 1994 Miller SM, Simon RJ, Ng S, Zuckermann RN, Kerr JM, Moos WH -
C-terminal cysteines of Tn501 mercuric ion reductase.
Biochemistry 1992 Moore MJ, Miller SM, Walsh CT -
Communication between the active sites in dimeric mercuric ion reductase: an alternating sites hypothesis for catalysis.
Biochemistry 1991 Miller SM, Massey V, Williams CH, Ballou DP, Walsh CT -
Use of a site-directed triple mutant to trap intermediates: demonstration that the flavin C(4a)-thiol adduct and reduced flavin are kinetically competent intermediates in mercuric ion reductase.
Biochemistry 1990 Miller SM, Massey V, Ballou D, Williams CH, Distefano MD, Moore MJ, Walsh CT -
Evidence for the participation of Cys558 and Cys559 at the active site of mercuric reductase.
Biochemistry 1989 Miller SM, Moore MJ, Massey V, Williams CH, Distefano MD, Ballou DP, Walsh CT -
Two-electron reduced mercuric reductase binds Hg(II) to the active site dithiol but does not catalyze Hg(II) reduction.
The Journal of biological chemistry 1986 Miller SM, Ballou DP, Massey V, Williams CH, Walsh CT -
Secondary isotope effects and structure-reactivity correlations in the dopamine beta-monooxygenase reaction: evidence for a chemical mechanism.
Biochemistry 1985 Miller SM, Klinman JP -
Magnitude of intrinsic isotope effects in the dopamine beta-monooxygenase reaction.
Biochemistry 1983 Miller SM, Klinman JP -
Deduction of kinetic mechanisms from primary hydrogen isotope effects: dopamine beta-monooxygenase--a case history.
Methods in enzymology 1982 Miller SM, Klinman JP