Susan Miller, PhD

Professor Emeritus WOS

Executive Committee Member

Department of Pharmaceutical Chemistry

Elisabeth Fall

[email protected]

600 16th St, Rm S512B

UCSF Box 2280

San Francisco, CA 94158

United States

Links

Miller Lab UCSF Profiles

Affiliations

What I do

Broadly, I 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. 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.

Departmental research area

chemical biology and medicinal chemistry

My research expertise

redox enzymology, mechanistic enzymology, flavoproteins, enzyme kinetics, protein structure/function, mercury biochemistry, mercury proteomics

Professional background

Biography

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. 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.

Research keywords

Enzyme mechanisms emphasizing redox systems
protein-protein interactions
structure-function relationships of mechanisms of regulation and catalysis
Candida albicans
Mercury
Metals, Heavy
Mercury Compounds
Metallochaperones
Cysteine
Receptors, Estrogen
bacteria
DNA Transposable Elements
Lyases
Kinetics
Bacillus
Mercury Isotopes
Oxidoreductases
Fungal Proteins

1.	Sigma Xi, University of California, 1984
2.	Phi Beta Kappa, University of Missouri, 1978
3.	Phi Lambda Upsilon, University of Missouri, 1977
4.	National Merit Scholar, 1974
5.	Curator's Scholar Award, University of Missouri, 1974

Publications

Kathryn D Bewley, Philip R Bennallack, Mark A Burlingame, Richard A Robison, Joel S Griffitts, Susan M Miller. Capture of micrococcin biosynthetic intermediates reveals C-terminal processing as an obligatory step for in vivo maturation. Proc Natl Acad Sci USA. 2016; 113(44):12450-12455.

Bennallack PR, Bewley KD, Burlingame MA, Robison RA, Miller SM, Griffitts JS. Reconstitution and Minimization of a Micrococcin Biosynthetic Pathway in Bacillus subtilis. J Bacteriol. 2016 09 15; 198(18):2431-8.

Pan S, Sommese RF, Sallam KI, Nag S, Sutton S, Miller SM, Spudich JA, Ruppel KM, Ashley EA. 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 Med Genet. 2015 Oct 26; 16:97.

LaVoie SP, Mapolelo DT, Cowart DM, Polacco BJ, Johnson MK, Scott RA, Miller SM, Summers AO. Organic and inorganic mercurials have distinct effects on cellular thiols, metal homeostasis, and Fe-binding proteins in Escherichia coli. J Biol Inorg Chem. 2015 Dec; 20(8):1239-51.

Lian P, Guo HB, Riccardi D, Dong A, Parks JM, Xu Q, Pai EF, Miller SM, Wei DQ, Smith JC, Guo H. 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 Nov 25; 53(46):7211-22.

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. Structure and dynamics of a compact state of a multidomain protein, the mercuric ion reductase. Biophys J. 2014 Jul 15; 107(2):393-400.

Sommese RF, Nag S, Sutton S, Miller SM, Spudich JA, Ruppel KM. 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; (8):e83403.

Riccardi D, Guo H-B, Parks JM, Gu B, Summers AO, Miller SM, Liang L, Smith JC.. Why Mercury Prefers Soft Ligands. J. Phys. Chem. Lett. 2013; (4):2317-2322.

Johs A, Harwood IM, Parks JM, Nauss RE, Smith JC, Liang L, Miller SM. Structural characterization of intramolecular Hg(2+) transfer between flexibly linked domains of mercuric ion reductase. J Mol Biol. 2011 Oct 28; 413(3):639-56.

Polacco BJ, Purvine SO, Zink EM, Lavoie SP, Lipton MS, Summers AO, Miller SM. Discovering mercury protein modifications in whole proteomes using natural isotope distributions observed in liquid chromatography-tandem mass spectrometry. Mol Cell Proteomics. 2011 Aug; 10(8):M110.004853.

Song B, Galande AK, Kodokula K, Moos WH, 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; 72:1-11.

Ledwidge R, Hong B, Dötsch V, Miller SM. NmerA of Tn501 mercuric ion reductase: structural modulation of the pKa values of the metal binding cysteine thiols. Biochemistry. 2010 Oct 19; 49(41):8988-98.

Hong B, Nauss R, Harwood IM, 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 Sep 21; 49(37):8187-96.

Guo HB, Johs A, Parks JM, Olliff L, Miller SM, Summers AO, Liang L, Smith JC. Structure and conformational dynamics of the metalloregulator MerR upon binding of Hg(II). J Mol Biol. 2010 May 14; 398(4):555-68.

Parks JM, Guo H, Momany C, Liang L, Miller SM, Summers AO, Smith JC. Mechanism of Hg-C protonolysis in the organomercurial lyase MerB. J Am Chem Soc. 2009 Sep 23; 131(37):13278-85.

Groban ES, Clarke EJ, Salis HM, Miller SM, Voigt CA. Kinetic buffering of cross talk between bacterial two-component sensors. J Mol Biol. 2009 Jul 17; 390(3):380-93.

Farady CJ, Sun J, Darragh MR, Miller SM, Craik CS. The mechanism of inhibition of antibody-based inhibitors of membrane-type serine protease 1 (MT-SP1). J Mol Biol. 2007 Jun 15; 369(4):1041-51.

Ledwidge R, Patel B, Dong A, Fiedler D, Falkowski M, Zelikova J, Summers AO, Pai EF, Miller SM. 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 Aug 30; 44(34):11402-16.

Ledwidge R, Soinski R, Miller SM. Direct monitoring of metal ion transfer between two trafficking proteins. J Am Chem Soc. 2005 Aug 10; 127(31):10842-3.

Vetriani C, Chew YS, Miller SM, Yagi J, Coombs J, Lutz RA, Barkay T. Mercury adaptation among bacteria from a deep-sea hydrothermal vent. Appl Environ Microbiol. 2005 Jan; 71(1):220-6.

Shimba N, Serber Z, Ledwidge R, Miller SM, Craik CS, Dötsch V. Quantitative identification of the protonation state of histidines in vitro and in vivo. Biochemistry. 2003 Aug 05; 42(30):9227-34.

Barkay T, Miller SM, Summers AO. Bacterial mercury resistance from atoms to ecosystems. FEMS Microbiol Rev. 2003 Jun; 27(2-3):355-84.

Serber Z, Ledwidge R, Miller SM, Dötsch V. Evaluation of parameters critical to observing proteins inside living Escherichia coli by in-cell NMR spectroscopy. J Am Chem Soc. 2001 Sep 19; 123(37):8895-901.

Serber Z, Keatinge-Clay AT, Ledwidge R, Kelly AE, Miller SM, Dötsch V. High-resolution macromolecular NMR spectroscopy inside living cells. J Am Chem Soc. 2001 Mar 14; 123(10):2446-7.

Buckman J, Miller SM. Stabilization of a novel enzyme.substrate intermediate in the Y206F mutant of Candida albicans EBP1: evidence for acid catalysis. Biochemistry. 2000 Aug 29; 39(34):10532-41.

Buckman J, Miller SM. Transient kinetics and intermediates formed during the electron transfer reaction catalyzed by Candida albicans estrogen binding protein. Biochemistry. 2000 Aug 29; 39(34):10521-31.

Cui W, DeWitt JG, Miller SM, Wu W. No metal cofactor in orotidine 5'-monophosphate decarboxylase. Biochem Biophys Res Commun. 1999 May 27; 259(1):133-5.

Samuels NM, Gibson BW, Miller SM. 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 May 11; 38(19):6195-203.

Engst S, 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 Mar 23; 38(12):3519-29.

Miller SM. Bacterial detoxification of Hg(II) and organomercurials. Essays Biochem. 1999; 34:17-30.

Buckman J, Miller SM. Binding and reactivity of Candida albicans estrogen binding protein with steroid and other substrates. Biochemistry. 1998 Oct 06; 37(40):14326-36.

Engst S, 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 Aug 18; 37(33):11496-507.

Wu W, Ley-han A, Wong FM, Austin TJ, Miller SM. Bioorg & Med Chem Lett. Decarboxylation of 1,3- Dimethylorotic Acid Revisited: Determining the Role of N-1. 1997; 7:2623-2628.

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 Oct 10; 34(40):13066-73.

Miller SM, Simon RJ, Ng S, Zuckermann, RN, Kerr JM, Moos WH. Drug Dev Res. Comparison of the Proteolytic Susceptabilities of Homologous L-Amino Acid, D-Amino Acid, and NSubstituted Glycine Peptide and Peptoid Oligomers. 1995; 35:20-32.

Arunachalam U, Massey V, Miller SM. Mechanism of p-hydroxyphenylacetate-3-hydroxylase. A two-protein enzyme. J Biol Chem. 1994 Jan 07; 269(1):150-5.

Miller SM, Simon RJ, Ng S, Zuckermann RN, Kerr JM, Moos WH. Bioorg & Med Chem Letters. Proteolytic Studies of Homologous Peptide and N-Substituted Glycine Peptoid Oligomers. 1994; 4:2657-2662.

Moore MJ, Miller SM, Walsh CT. C-terminal cysteines of Tn501 mercuric ion reductase. Biochemistry. 1992 Feb 18; 31(6):1677-85.

Miller SM, Massey V, Williams CH, Ballou DP, Walsh CT. Communication between the active sites in dimeric mercuric ion reductase: an alternating sites hypothesis for catalysis. Biochemistry. 1991 Mar 12; 30(10):2600-12.

Miller SM, Massey V, Ballou D, Williams CH, Distefano MD, Moore MJ, 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 Mar 20; 29(11):2831-41.

Miller SM, Moore MJ, Massey V, Williams CH, Distefano MD, Ballou DP, Walsh CT. Evidence for the participation of Cys558 and Cys559 at the active site of mercuric reductase. Biochemistry. 1989 Feb 07; 28(3):1194-205.

Miller SM, Ballou DP, Massey V, Williams CH, Walsh CT. Two-electron reduced mercuric reductase binds Hg(II) to the active site dithiol but does not catalyze Hg(II) reduction. J Biol Chem. 1986 Jun 25; 261(18):8081-4.

Miller SM, Klinman JP. Secondary isotope effects and structure-reactivity correlations in the dopamine beta-monooxygenase reaction: evidence for a chemical mechanism. Biochemistry. 1985 Apr 23; 24(9):2114-27.

Miller SM, Klinman JP. Magnitude of intrinsic isotope effects in the dopamine beta-monooxygenase reaction. Biochemistry. 1983 Jun 21; 22(13):3091-6.

Miller SM, Klinman JP. Deduction of kinetic mechanisms from primary hydrogen isotope effects: dopamine beta-monooxygenase--a case history. Methods Enzymol. 1982; 87:711-32.