MetalloBiomolecule Interest Group (MBIG)

    MBIG is kind of a namesake of MPIG (MetelloProtein Interest Group) at the University of Minnesota where I spent 3 years as a postdoc working on iron proteins (including Fe-superoxide dismutase, isopenicillin N synthase, purple acid phosphatases, and ribonucleotide reductase) and Fe complexes (including Fe-bleomycin and synthetic Fe complexes) in Professor Lawrence Que's group.  To reflect the projects that we have been working on in the group, i.e., metalloproteins,  metalloantibiotics, metallopeptides, metal-centered hydrolysis, and  metal-DNA chemistry, the acronym MBIG (MetalloBiomolecule Interest Group) finally came out that everyone liked.  Here is a list of the group members in the MBIG:

Current Members:
Graduate students:
Vasiliki Lykourinou-Tibbs
, who has been working on homogeneous and heterogeneous catalyses, including the hydrolysis and oxidation chemistry of metalloresins and metallopolymers. The results from the study of the oxidative activities of metallopolymers suggest a catechol oxidase-like mechanism for the catalysis.  This mechanism seems to be also applicable to the oxidation activity of metallopeptides observed in our group.
   Lykourinou-Tibbs, V.; Ercan, A.; Ming, L.-J. “Iron(III)-Chelex Resin Complex as a Prototypical Heterogeneous Catalyst for Phosphoester Hydrolysis” Catal. Commun. 2003, 4, 549–553.  (abstract )
   Hanafy, A. I.; Lykourinou-Tibbs, V.; Bisht, K. S. Ming, L.-J. “Effective Heterogeneous Hydrolysis of Phosphodiester by Pyridine-Containing Metallopolymers” Inorg. Chim. Acta. 2005, 358, 1247–1252. (abstract )

Giordano da Silva has been working on the expression of a metalloprotease (BP10) from the sea urchin embryos during the blastura stage.  BP10 contains an active domain analogous to astacin. The cDNA has been inserted into bacterial plasmid and the whole protein and a truncated protein of the active domain have been expressed in active forms and their kinetic behaviors determined.  In the meantime, Gio is using his excellent molecular biology skills to clone and express the aminopeptidase from Streptomyces.  Other than molecular biology, Gio is very familiar in kinetics of enzymes and biomimetic systems.  The study of the oxidative activity of metallo-β-amylopid has yielded interesting results which allow a catechol oxidase-like mechanism of the catalysis to be proposed.  
   da Silva, G. F. Z.; Tay, W. M.; Ming, L.-J. “Catechol Oxidase-Like Oxidation Chemistry of the 1–20 and 1–16 Fragments of Alzheimer’s Disease-Related β-Amyloid Peptide: Their Structure-Activity Correlation and the Fate of Hydrogen Peroxide” J. Biol. Chem. 2005, 280, 16601-16609. (abstract)
   da Silva, G. F. Z.; Tay, W. M.; Ming, L.-J. “Alzheimer’s Disease-Related Copper(II)-β-Amyloid Peptide Exhibits Phenol Monooxygenase and Catechol Oxidase Activities” Angew. Chem. 2005, in press.  (abstract)

William Tay has focused on NMR study of metallobiomolecules.  He is currently working on structural assignment of metallobacitracin and metallo-β-amyloids.  William is also using kinetic methods to the the study of the magnetically coupled di-Cu derivative of Streptomyces aminopeptidase and phenol/polyphenol oxidation by metallopeptides.
   da Silva, G. F. Z.; Tay, W. M.; Ming, L.-J. “Catechol Oxidase-Like Oxidation Chemistry of the 1–20 and 1–16 Fragments of Alzheimer’s Disease-Related β-Amyloid Peptide: Their Structure-Activity Correlation and the Fate of Hydrogen Peroxide” J. Biol. Chem. 2005, 280, 16601-16609. (abstract

Kashmir Junaja has been working on kinetic study of the hydrolytic catalysis by metallopolymers.  His thesis project will focus on kinetic and thermodynamic studies of the hydrolytic and oxidative activities of some metallopeptides designed on the basis of the metal-binding motifs of metalloenzymes.

Undergraduates:
Regina Maldonado has been working on the hydrolytic chemistry of pyridine and amide-containing metallopolymers as her honors thesis project.
John O'Leary has been working on the inhibition of prolidase by anticancer anthracycline drugs.  He double-majors in Music and Chemistry and he plays the piano and the tuba.
Morgan Courty has been working on the hydrolytic chemistry of pyridine and carboxylate-containing metallopolymers as his hornors thesis.
Ariana Namdari  has been working on the hydrolytic chemistry of pyridine and phenyl-containing metallopolymers.
Chien-Yi (Erin) Wu has been working on the characterization of the Ni(II) derivative of Streptomyces aminopeptidase.
Xenia Wallicey has been working on the oxidation chemistry of pyridine and amide-containing metalloporphyrin-polymers complexes.
William has been working on overexpression of Streptomyces aminopeptidase.

Former Graduate Students:
Xiangdong (David) Wei, Ph.D. (now at Washington Mutual, Chicago), who was working on the antitumor antibiotics anthracyclines and streptonigrin and on the heme domain of nitrate reductase.
    Awards:
Summer Fellowship, Institute for Biomolecular Science, USF (1994, 1995)
Departmental "Ashford Award" for outstanding graduate student (1995)
    Publications:
    Ming, L.-J.; Wei, X. "An Ytterbium(III) Complex of Daunomycin, a Model Metal Complex of Anthracycline Antibiotics" Inorg. Chem. 1994, 33, 4617-4618.  (abstract 5)
    Wei, X; Ming, L.-J.; Cannons, A. C.; Solomonson, L. P. "1H and 13C NMR Studies of a Truncated Heme Domain from Chlorella vulgaris Nitrate Reductase:  Signal Assignment of the Heme Moiety" Biochim. Biophys. Acta 1998, 1382, 129-136.  (abstract 11)
    Wei, X.; Ming, L.-J. "Comprehensive 2D 1H NMR Studies of Paramagnetic Lanthanide(III) Complexes of Anthracycline Antitumor Antibiotics" Inorg. Chem. 1998, 37, 2255-2262.  (abstract 12)
    Wei, X.; Ming, L.-J.* "NMR Studies of Metal Complexes and DNA Binding of the Quinone-Containing Antibiotic Streptonigrin" J. Chem. Soc. Dalton Trans. 1998, 2793-2798.  (abstract 15)

Jon Epperson, Ph.D., (postdoc at Department of Chemistry, Florida State University; then to George Washington Universty pursuing a law degree) who was working on the use of paramagnetic metal ions as NMR probes for the study of the metalloantibiotic peptide bacitracin and derivatives, tri-Zn phospholipase C, and metallodendrimers.
    Awards:
Summer Fellowship, Institute for Biomolecular Science, USF (1994, 1995)
USF Graduate Council Outstanding Dissertation Award (2000)
   Publication:
    Epperson, J. D.; Ming, L.-J.; Woosley, B. D.; Baker, G. R.; Newkome, G. R. "Analyzing the Infrastructure of Dendritic Macromolecules Using a Paramagnetic Metal Ion NMR Probe"  Inorganic Chemistry 1999, 38, 4498-4502. (abstract 19)
    Epperson, J. D.; Ming, L.-J. "Proton NMR Studies of Co(II) Complexes of Bacitracin Analogous —Insight into Structure-Activity Relationship" Biochemistry 2000, 39, 4037–4045. (abstract 23)
    Epperson, J. D.; Ming, L.-J. "Binding of Cobalt(II) and Copper(II) to Trinuclear Phospholipase C from Bacillus cereus— A Novel 1H NMR Spectrum of a “Tri-Cu(II)” Center in Protein" J. Inorg. Biochem. 2001, 87, 149-156. ( abstract 27)
    Epperson, J. D.; Ming, L.-J.; Baker, G. R.; Newkome, G. R. "Paramagnetic Cobalt(II) as an NMR Probe for Dendrimer Structure, Mobility, and Coorperativity" J. Am. Chem. Soc.  2001, 123, 8583–8592. (abstract 28)
    Ming, L.-J.; Epperson, J. D. "Metal Binding and Structure–Activity Relationship of the Metalloantibiotic Peptide Bacitracin" J. Inorg. Biochem. (a focused review) 2002, 91, 46–58 (abstract 30)

Hyun Ik Park, Ph.D. (was an NSF postdoctoral fellow and an American Heart Association Postdoctoral Fellow at the Department of Chemistry of Florida State University, currently at R&D Systems at Minneapolis ), who was working on the unique metalloendopeptidase astacin from crayfish and on mechanistic study of Streptomyces griseus aminopeptidase.
    Awards:
Outstanding Student Presentation Award, ACS Annual Meeting of the Florida Section, 1995
Summer Fellowship, Institute for Biomolecular Science, USF (1995)
Departmental "Ashford Award" for outstanding graduate student (1999)
Departmental "Tharp Publication Award" (1999)
    Publications:
    Lin, L.-Y.; Park, H. I.; Ming, L.-J. "Metal Binding and Active Site Structure of Di-Zinc Streptomyces griseus Aminopeptidase" J. Biol. Inorg. Chem. 1997, 2, 744-749.  (abstract 10)
    Park, H. I.; Ming, L.-J. "The Mechanistic Role of the Coordinated Tyr in Astacin" J. Inorg. Biochem. 1998, 72, 57-62.  (abstract 16)
    Park, H. I.; Ming, L.-J. "A Novel 1010 Rate Enhancement of Phosphodiester Hydrolysis by a Di-Zinc Aminopeptidase– Transition State Analogues as Substrates?" Angew. Chem. Intl. Engl. Ed. 1999, 38, 2914-2916. (abstract 21)
    Hasselgren, C.; Park, H. I.; Ming, L.-J. "Metal Ion Binding and Activation of Streptomyces griseus Aminopeptidase —Cadmium(II) Binding as a Model" J. Biol. Inorg. Chem. 2001, 6, 120–127. (abstract 24)
    Ercan, A.; Park, H. I.; Ming, L.-J. "Remarkable Enhancement of the Hydrolyses of Phosphoesters by Dimetal Centers —Streptomyces Aminopeptidase as a “Natural Model System”" Chem. Commun. 2000, 2501–2502.  (abstract 25)
    Park, H. I.; Ming, L.-J. "Mechanistic Studies of the Astacin-like Serratia Metalloendopeptidase Serralysin —Highly Active (>2,000%) Co(II)- and Cu(II)-Substituted Derivatives for Further Corroboration of a 'Metallotriad' Mechanism" J. Biol. Inorg. Chem. 2002, 7, 600–610.  (abstract 29)

Jason Palcic, Ph. D. (postdoctoral reserach/lecturer at  the Department of Chemistry, University of Memphis and is now the Chemical Terrarism Coordinator at the Florida Department of Health), who has been working on the use of 2D NMR techniques for the study of paramagnetic mitramycin-Co(II)-DNA complexes which exhibit "high resolution" hyperfine-shifted 1H NMR spectra, and on P-31 NMR study of nitrate reductase.
    Publication:
Palcic, J. D.; Ming, L.-J.; Barber, M. J. “31P NMR Spectroscopy of the Flavin Domain of Assimilatory Nitrate Reductase” in preparation
Palcic, J. D.; Ming, L.-J. "'High Resolution" 1H NMR Study of Paramagnetic Metallobiomolecules:  Mithramycin-Co(II)-DNA ternary complex as an Example" in preparation

Craig Bertolucci, Ph. D. (did postdoctoral research at the Department of Biochemistry, the Ohio State University as a postdoctoral associate and is now at the St. Jude Children's Hospital), who has been working on the use of paramagnetic metal ions as NMR probes for the study of the metalloproteins parvalbumin, FixL kinase, and di-Zn aminopeptidase.
    Awards:
Summer Fellowship, Institute for Biomolecular Science, USF (1995)
Departmental "Outstanding First-Year Graduate Student" Award (1994)
Departmental "Ashford Award" for outstanding graduate student (1997)
    Publication:
    Bertolucci, C.; Ming, L.-J.; Gonzalez, G.; Gilles-Gonzalez, M. A. "Assignment of the Hyperfine-Shifted 1H NMR Signals of the Heme in the Oxygen Sensor FixL from Rhizobium metiloti" Chem. Biol. 1996, 3, 561-566.  (abstract 8)
    Harris, M. N.; Bertolucci, C. M.; Ming, L.-J. "Paramagnetic Cobalt(II) as a Probe for Kinetic and NMR Relaxation Studies of Phosphate Binding and Catalytic Mechanism of Streptomyces Dinuclear Aminopeptidase" Inorganic Chemistry 2002, 41, 5582-5588. (abstract 31)

Michael Harris
, Ph.D. (did postdoctoral research at the University of New Mexico and is not a postdoc/research chemist at the Los Alamos National Laboratory) who has been studying metal binding and activation of Streptomyces griseus aminopeptidase as well as inhibition study of this enzyme.
    Award:
Departmental "Tharp Publication Award" (2000)
    Publication:
    Harris, M. N.; Ming, L.-J. "Different Phosphate Binding Modes of Streptomyces griseus Aminopeptidase between Crystal and Solution States and the Status of Zinc-Bound Water" FEBS Lett. 1999, 455, 321-324. (abstract 22)
    Harris, M. N.; Madura, J. D.; Ming, L.-J.; Harwood, V. J. "Kinetic and Mechanistic Studies of Prolyl Oligopeptidase from the Hyperthermophile  Pyrococcus furiosus" J. Biol. Chem. 2001, in press (abstract 26)
    Harris, M. N.; Bertolucci, C. M.; Ming, L.-J. "Paramagnetic Cobalt(II) as a Probe for Kinetic and NMR Relaxation Studies of Phosphate Binding and Catalytic Mechanism of Streptomyces Dinuclear Aminopeptidase" Inorganic Chemistry 2002, 41, 5582-5588. (abstract 31)

Altan Ercan
, Ph.D. (Now a postdoctoral researcher at the Department of Biochemistry and Molecular Biology of the University of Oklahoma) who was working on the mechanism of Streptomyces griseus aminopeptidase and its alternative catalysis toward phosphodiesters and studying metal binding and activation of dinuclear prolidase..
    Award:
Departmental "Tharp Publication Award"
    Publication:
    Ercan, A.; Park, H. I.; Ming, L.-J. "Remarkable Enhancement of the Hydrolyses of Phosphoesters by Dimetal Centers —Streptomyces Aminopeptidase as a “Natural Model System”" Chem. Commun. 2000, 2501–2502.  (abstract 25)
    Lykourinou-Tibbs, V.; Ercan, A.; Ming, L.-J. “Iron(III)-Chelex Resin Complex as a Prototypical Heterogeneous Catalyst for Phosphoester Hydrolysis” Catal. Commun. 2003, 4, 549–553.  (abstract 33)

Hong-Chu Yang (went to Emory University pursuing Ph.D.), worked on NMR study of Yb(III)-substituted parvalmunin.

Lung-Yu (Victor) Lin (M.S., now at Unilever, Taiwan), who was working on metal binding and activation of Streptomyces griseus aminopeptidase.
    Publication:
    Lin, L.-Y.; Park, H. I.; Ming, L.-J. "Metal Binding and Active Site Structure of Di-Zinc Streptomyces griseus Aminopeptidase" J. Biol. Inorg. Chem. 1997, 2, 744-749.  (abstract 10)

Visitors from other Institutions
Ahmed Hanafy, Ph.D. (from Egypt), who was working on the hydrolytic and oxidative activities of Cu-binding polymers.
   Hanafy, A. I.; Lykourinou-Tibbs, V.; Bisht, K. S. Ming, L.-J. “Effective Heterogeneous Hydrolysis of Phosphodiester by Pyridine-Containing Metallopolymers” Inorg. Chim. Acta. 2005, 358, 1247–1252. (abstract )

Former Undergraduate students
Students with thesis:
Rosemary Keene
(now in the medical school at USF), studied and contributed to "Phosphate inhibition of Streptomyces griseus Aminopeptidase (abstract 22)" as her honors thesis project.
 
Catrin Hasselgren (Completed her Ph.D. at the Department of Inorganic Chemistry, Chalmers University of Technology, Sweden, 2002 and is now a postdoctoral researcher at AstraZeneca in Sweden) worked on Cd(II) binding and activation of Streptomyces griseus Aminopeptidase.
    Publication:
    Hasselgren, C.; Park, H. I.; Ming, L.-J. "Metal Ion Binding and Activation of Streptomyces griseus Aminopeptidase —Cadmium(II) Binding as a Model" J. Biol. Inorg. Chem. 2001, 6, 120–127. (abstract 25)

Kashmir Junaja (Completed MA in Chemistry in 3 years, and is now in the graduate program here) worked on hydrolytic chemistry of metallopolymers as his honors thesis project.

Students without thesis:
Yohji Fukazawa (1994), Jurgen Thias (1995), Thu Luu (1996) a University Minority Scholar, Vasiliki Likourinou (1999/2000), Syed Hussain (2000); Vinh Phan (2001), Giordano da Silva (2001/2002), Jennifer Wellborn Brillant (2003), Rani Dadlani (2003), Dieu Thu Thi Nguyen (2003) a University Minority Scholar, Elizabeth Villarroel (2003/2004)
 
Former high school students in the Summer BioMed Program who worked in the lab:
1992
Kattron Rodes, East Bay High (parvalbumin purification)

1993
Ingrid Lim, Hillsborough High (purification of blue copper protein from spinach leaves)
Mandeep Dhala, Zephyrhills High (purification of blue copper protein from spinach leaves)

1994
Shanti Singh, Gaither HS (protein purification)
Katherine Lowther, Lake 'O Lake HS (protein purification)
Joe Thomas, Carninal Mooney HS (protein purification)

1995
Victor Chang, Jesuit High (protein purification)
Katherine Frost, Leto High (protein purification)
Pei-Jen Hwang, Tampa Bay Tech (protein purification)

1996
Pavan Cheruvu, Hillsborough High  (metal activation of serralysin)  He won the second place at the County Science Fair and the sixth place at state competition on inhibition study of Streptomyces aminopeptidase.
Reena Ninan, King HS (metal activation of serralysin)

1997
Jashleen Bedi (metal influence on aminopeptidase activity)

1998
Becky Konnerth, Andrew Kuo, Akshata Marballi, and Michelle Ming  (inhibition study of aminopeptidase, and were acknowledged in the publication Harris, M. N.; Ming, L.-J. "Different Phosphate Binding Modes of Streptomyces griseus Aminopeptidase between Crystal and Solution States and the Status of Zinc-Bound Water"  FEBS Lett. 1999 , 455, 321-324. abstract 22)

1999
Mary Chen, King HS (Inhibition Studies of Metalloaminopeptidase)

2000
Mary Chen (Inhibition of Metalloaminopeptidase by the Antibiotic Bacitracin—Alternative Biological Activity of Bacitracin?)
Ashwini Momarla (Hydrolytic Reactions by Metallobacitracin—Alternative Biological Activity of Metalloantibiotics?) 

2002
Aswini Komarla, Anupama Kotha, Kara Brown, and Jane Zhu (involved in initial research on metallopolymer chemistry, and were acknowledged in Hanafy, A. I.; Lykourinou-Tibbs, V.; Bisht, K. S. Ming, L.-J. “Effective Heterogeneous Hydrolysis of Phosphodiester by Pyridine-Containing Metallopolymers” Inorg. Chim. Acta. 2005, 358, 1247–1252. abstract )