Research Topics
| Gregory VerdineSummaryAffiliation: Harvard University Country: USA Publications
Research Grants
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Detail Information
Publications
Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helixLoren D Walensky
Howard Hughes Medical Institute, Department of Pediatric Hematology Oncology and Children s Hospital Boston, Massachusetts, USA
Science 305:1466-70. 2004..Hydrocarbon stapling of native peptides may provide a useful strategy for experimental and therapeutic modulation of protein-protein interactions in many signaling pathways...
A superhelical spiral in the Escherichia coli DNA gyrase A C-terminal domain imparts unidirectional supercoiling biasAlexander J Ruthenburg
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA
J Biol Chem 280:26177-84. 2005..We propose a model wherein the right-handed ((+) solenoidal) wrapping of DNA around the E. coli GyrA-CTD enforces unidirectional (-) DNA supercoiling...- A stapled BID BH3 helix directly binds and activates BAXLoren D Walensky
Department of Pediatric Oncology, Dana Farber Cancer Institute and Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA
Mol Cell 24:199-210. 2006..We further demonstrate that membrane targeting of stapled BID BH3 optimizes its ability to activate BAX, supporting a model in which BID directly engages BAX to trigger mitochondrial apoptosis... - Trapping distinct structural states of a protein/DNA interaction through disulfide crosslinkingChuan He
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
Chem Biol 9:1297-303. 2002..Here, we describe the development of an approach to trap both sequence-specific and nonsequence-specific DNA recognition complexes of N-Ada through formation of an intermolecular disulfide crosslink between the protein and DNA... - Covalent trapping of protein-DNA complexesGregory L Verdine
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Annu Rev Biochem 72:337-66. 2003..In recent years, strategies developed for the covalent trapping of protein-DNA complexes have begun to show promise as a window into an otherwise inaccessible world of structure... - The challenge of drugging undruggable targets in cancer: lessons learned from targeting BCL-2 family membersGregory L Verdine
Department of Chemistry and Chemical Biology, and Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
Clin Cancer Res 13:7264-70. 2007.... - Structural basis for removal of adenine mispaired with 8-oxoguanine by MutY adenine DNA glycosylaseJ Christopher Fromme
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Nature 427:652-6. 2004..These structures reveal the basis for recognizing both lesions in the A*oxoG pair and for catalysing removal of the adenine base... - Structure of a repair enzyme interrogating undamaged DNA elucidates recognition of damaged DNAAnirban Banerjee
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA
Nature 434:612-8. 2005..The structure reveals a remarkably effective gate-keeping strategy for lesion discrimination and suggests a mechanism for oxoG insertion into the hOGG1 active site... - Direct inhibition of the NOTCH transcription factor complexRaymond E Moellering
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Nature 462:182-8. 2009..Direct antagonism of the NOTCH transcriptional program causes potent, NOTCH-specific anti-proliferative effects in cultured cells and in a mouse model of NOTCH1-driven T-ALL... - Structure of a trapped endonuclease III-DNA covalent intermediateJ Christopher Fromme
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
EMBO J 22:3461-71. 2003..This structure also suggests a rationale for the frequent occurrence in certain human cancers of a specific mutation in the related DNA repair protein MYH... - Structural insights into lesion recognition and repair by the bacterial 8-oxoguanine DNA glycosylase MutMJ Christopher Fromme
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Nat Struct Biol 9:544-52. 2002..These structures reveal that the MutM active site performs the multiple steps of base-excision and 3' and 5' nicking with minimal rearrangement of the DNA backbone... - Structure of a DNA glycosylase searching for lesionsAnirban Banerjee
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA
Science 311:1153-7. 2006..MutM therefore actively interrogates the intact DNA helix while searching for damage... - Nucleotide-dependent domain movement in the ATPase domain of a human type IIA DNA topoisomeraseHua Wei
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA
J Biol Chem 280:37041-7. 2005..Comparison of these structures revealed rigid-body movement of the structural modules within the ATPase domain, suggestive of the motions of a molecular gate... - Structural characterization of human 8-oxoguanine DNA glycosylase variants bearing active site mutationsChristopher T Radom
Department of Chemistry, Harvard University, Cambridge, Massachusetts 02138, USA
J Biol Chem 282:9182-94. 2007..The latter structure offers a view of the latest stage in the base extrusion pathway yet observed, and its lack of catalytic activity demonstrates that the transition state for displacement of the lesion base is geometrically demanding... 
Stereochemical effects of all-hydrocarbon tethers in i,i+4 stapled peptidesYoung Woo Kim
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
Bioorg Med Chem Lett 19:2533-6. 2009..These results suggest that the vesicular trafficking pathway employed by cells to take up stapled peptides is sensitive to the extent of helical character in the peptide, with greater helicity conferring increased cellular uptake...- Nonspecifically bound proteins spin while diffusing along DNAPaul C Blainey
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA
Nat Struct Mol Biol 16:1224-9. 2009..The average free-energy barrier for sliding along the DNA was 1.1 +/- 0.2 k(B)T. Such small barriers facilitate rapid search for binding sites... - Structure of the E. coli DNA glycosylase AlkA bound to the ends of duplex DNA: a system for the structure determination of lesion-containing DNABrian R Bowman
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA
Structure 16:1166-74. 2008..The structures of 8-oxoguanine provide a correct atomic-level view of this important endogenous lesion in DNA... - 5-amino-2'-deoxyuridine, a novel thymidine analogue for high-resolution footprinting of protein-DNA complexesMichael J Storek
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Org Lett 4:3867-9. 2002..The performance of 5-amino-dU in interference footprints is similar to that of the previously described analogue 5-hydroxy-dU, but the former is incorporated more readily into DNA during enzymatic polymerization... - Synthesis and structure of duplex DNA containing the genotoxic nucleobase lesion N7-methylguanineSeongmin Lee
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA
J Am Chem Soc 130:11570-1. 2008..These observations suggest that AlkA and Aag must perform a structurally invasive interrogation of DNA in order to detect the presence of intrahelical m7dG lesions... - Reactivation of the p53 tumor suppressor pathway by a stapled p53 peptideFederico Bernal
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA
J Am Chem Soc 129:2456-7. 2007 - Trapping and structural elucidation of a very advanced intermediate in the lesion-extrusion pathway of hOGG1Seongmin Lee
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA
J Am Chem Soc 130:7784-5. 2008.... - Crystal structure of Bacillus stearothermophilus UvrA provides insight into ATP-modulated dimerization, UvrB interaction, and DNA bindingDanaya Pakotiprapha
Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA
Mol Cell 29:122-33. 2008..Structural analysis, biochemical experiments, surface electrostatics, and sequence conservation form the basis for models of ATP-modulated dimerization, UvrA-UvrB interaction, and DNA binding during the search for lesions... - A structural model for the damage-sensing complex in bacterial nucleotide excision repairDanaya Pakotiprapha
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
J Biol Chem 284:12837-44. 2009..The crystal structure and accompanying biochemical analyses suggest a model for the complete damage-sensing complex... - Histone H3 recognition and presentation by the WDR5 module of the MLL1 complexAlexander J Ruthenburg
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA
Nat Struct Mol Biol 13:704-12. 2006..Contrary to predictions, the structures reveal that WDR5 does not read out the methylation state of K4 directly, but instead serves to present the K4 side chain for further methylation by SET1-family complexes... - A base-excision DNA-repair protein finds intrahelical lesion bases by fast sliding in contact with DNAPaul C Blainey
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
Proc Natl Acad Sci U S A 103:5752-7. 2006..5 kcal/mol (1 kcal = 4.2 kJ). This nearly barrierless Brownian sliding indicates that DNA glycosylases locate lesion bases by a massively redundant search in which the enzyme selectively binds 8-oxoguanine under kinetic control... - Structural and biochemical exploration of a critical amino acid in human 8-oxoguanine glycosylaseDerek P G Norman
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA
Biochemistry 42:1564-72. 2003..Crystal structures of these mutants complexed with an unreactive abasic site in DNA reveal these residues to adopt a sterically disfavored helix-capping conformation... - Structures of end products resulting from lesion processing by a DNA glycosylase/lyaseSang J Chung
Department of Chemistry and Chemical Biology, Cambridge, Massachusetts 02138, USA
Chem Biol 11:1643-9. 2004..The resulting structure is consistent with the currently accepted catalytic mechanism for the protein. Unexpectedly, however, soaking of a nucleobase analog into the crystals results in religation of the DNA backbone in situ... - Product-assisted catalysis in base-excision DNA repairJ Christopher Fromme
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Nat Struct Biol 10:204-11. 2003..To our knowledge, the present example represents the first documented case of product-assisted catalysis in an enzyme-catalyzed reaction... - A methylation-dependent electrostatic switch controls DNA repair and transcriptional activation by E. coli adaChuan He
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
Mol Cell 20:117-29. 2005..The structures reveal that both phosphotriester repair and methylation-dependent transcriptional activation function through a zinc- and methylation-dependent electrostatic switch... - Crystal structure of Staphylococcus aureus tRNA adenosine deaminase TadA in complex with RNAHeather C Losey
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Nat Struct Mol Biol 13:153-9. 2006.... - High-resolution footprinting of sequence-specific protein-DNA contactsMichael J Storek
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA
Nat Biotechnol 20:183-6. 2002..Here we report a straightforward, high-resolution biochemical method for mapping, at single-nucleotide resolution, DNA bases that are subject to sequence-specific contacts by regulatory proteins... - Direct visualization of a DNA glycosylase searching for damageLiwei Chen
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
Chem Biol 9:345-50. 2002..These findings indicate that hOGG1 actively distorts DNA while searching for damaged bases... - All-atom model for stabilization of alpha-helical structure in peptides by hydrocarbon staplesPeter S Kutchukian
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA
J Am Chem Soc 131:4622-7. 2009..Finally, we critically investigate why our method works, exposing the underlying physical forces that stabilize stapled peptides... - Converting the sacrificial DNA repair protein N-ada into a catalytic methyl phosphotriester repair enzymeChuan He
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford St, Cambridge, Massachusetts 02138, USA
J Am Chem Soc 125:1450-1. 2003..Mutation of the active-site residue Cys38 of N-Ada converts it from a sacrificial DNA repair protein to an enzyme that uses methanethiol as an external sacrificial reagent to repair DNA methyl phosphotriesters catalytically... - Atomic substitution reveals the structural basis for substrate adenine recognition and removal by adenine DNA glycosylaseSeongmin Lee
Departments of Stem Cell and Regenerative Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
Proc Natl Acad Sci U S A 106:18497-502. 2009.... - DNA lesion recognition by the bacterial repair enzyme MutMJ Christopher Fromme
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
J Biol Chem 278:51543-8. 2003..Furthermore, the structure of MutM in complex with DNA containing an alternative substrate, dihydrouracil, demonstrates how MutM is able to recognize lesions other than oxoG... - DNA glycosylase recognition and catalysisJ Christopher Fromme
Department of Molecular and Cellular Biology, and Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
Curr Opin Struct Biol 14:43-9. 2004..A novel disulfide cross-linking strategy was used to obtain the long-anticipated structure of MutY bound to DNA containing an A*oxoG mispair... - Structure of human cytidine deaminase bound to a potent inhibitorSang J Chung
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA
J Med Chem 48:658-60. 2005..The structure reveals that inhibitor 1 is able to establish a canonical pi/pi-interaction with a key active site residue, Phe 137... - A nucleobase lesion remodels the interaction of its normal neighbor in a DNA glycosylase complexAnirban Banerjee
Department of Chemistry, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
Proc Natl Acad Sci U S A 103:15020-5. 2006..The extruded but intrahelical state of the G in this structure offers a view of an early intermediate in the base-extrusion pathway... - Introduction of all-hydrocarbon i,i+3 staples into alpha-helices via ring-closing olefin metathesisYoung Woo Kim
Department of Chemistry, Harvard University, Cambridge, Massachusetts 02138, USA
Org Lett 12:3046-9. 2010..The i,i+3 stapling system established here provides a potentially useful alternative to the well-established i,i+4 stapling system now in widespread use... - The human cytomegalovirus UL44 C clamp wraps around DNAGloria Komazin-Meredith
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
Structure 16:1214-25. 2008..The results of mutational and crosslinking studies were consistent with this model. Thus, UL44 is a "hybrid" of UL42 and PCNA: its structure is intermediate between the two and its mode of interaction with DNA has elements of both... - Structure and specificity of the vertebrate anti-mutator uracil-DNA glycosylase SMUG1Jane E A Wibley
Cancer Research UK DNA Repair Enzyme Group, Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, United Kingdom
Mol Cell 11:1647-59. 2003..This structure indicates a more invasive interaction with dsDNA than observed with other UDGs and reveals an elegant water displacement/replacement mechanism that allows SMUG1 to exclude thymine from its active site while accepting HmU... - The positively charged surface of herpes simplex virus UL42 mediates DNA bindingGloria Komazin-Meredith
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA
J Biol Chem 283:6154-61. 2008..Our results taken together strongly suggest that the basic back face of UL42 contacts DNA and that positive charge on this surface is important for this interaction... - Regulation of MLL1 H3K4 methyltransferase activity by its core componentsYali Dou
Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, New York 10021, USA
Nat Struct Mol Biol 13:713-9. 2006..Mechanistic insights gained from this study can be generalized to the whole family of SET1-like histone methyltransferases in mammals...
Research Grants
- FUNCTIONALLY TETHERED OLIGONUCLEOTIDESGregory Verdine; Fiscal Year: 2006..The proposed studies aim to illuminate the recombinase reaction mechanism in detail. ..
- Structure and Mechanism of Base-Excision DNA RepairGregory Verdine; Fiscal Year: 2007..Finally, we propose to extend our understanding of structure/function in BER to include the MutY protein, which functions in eukaryotes and prokaryotes to correct the mutagenic damage resulting from misreplication of 8-oxoguanine. ..
- FUNCTIONALLY TETHERED OLIGONUCLEOTIDESGregory Verdine; Fiscal Year: 2007..Our studies will focus on understanding how DNA cytosine methyltransferases (DCMTases) target particular cytosine residues in DNA for extrusion from the DNA helix and insert them into the extrahelical active site on the enzyme. ..
- Structure and Mechanism in DNA Excision RepairGregory Verdine; Fiscal Year: 2009..How such enzymes locate their diverse array of lesions and catalyze removal is poorly understood at the molecular level; it is the goal of the proposed program to fill in that substantial missing piece of the cancer puzzle. ..
- Structure and Mechanism in DNA Excision RepairGregory L Verdine; Fiscal Year: 2010..How such enzymes locate their diverse array of lesions and catalyze removal is poorly understood at the molecular level;it is the goal of the proposed program to fill in that substantial missing piece of the cancer puzzle. ..
- FUNCTIONALLY TETHERED OLIGONUCLEOTIDESGregory L Verdine; Fiscal Year: 2010..Our studies will focus on understanding how DNA cytosine methyltransferases (DCMTases) target particular cytosine residues in DNA for extrusion from the DNA helix and insert them into the extrahelical active site on the enzyme. ..
- FUNCTIONALLY TETHERED OLIGONUCLEOTIDESGregory Verdine; Fiscal Year: 1993....
- FUNCTIONALLY TETHERED OLIGONUCLEOTIDESGregory Verdine; Fiscal Year: 2002..The proposed experiments aim to resolve key issues regarding the DNA-binding mode of HMG-I(Y) and the mechanism by which it stimulates transactivation of the interferon-beta promoter by NF-kappaB. ..
- Structure and Mechanism in DNA Excision RepairGregory L Verdine; Fiscal Year: 2011..How such enzymes locate their diverse array of lesions and catalyze removal is poorly understood at the molecular level;it is the goal of the proposed program to fill in that substantial missing piece of the cancer puzzle. ..