Prof. Guang ZHU
My laboratory is interested in studying structure and function of proteins, DNA and RNA that play
important roles in cell cycle and in cancer with use of multidisciplinary approaches, especially the
biophysical methods, such as NMR spectroscopic method. Based on the structural knowledge obtained
from our research, we will search and design chemicals that can inhibit these proteins and can possibly
provide the treatment for various cancers. We are also interested in developing NMR technology to tackle
difficult biological problem. Currently, we are focusing on structure functional study of proteins and G-
quadruplex DNA involved in regulation and epigenetic control of genomic DNA replication.
Structural study of proteins in the initiation of DNA replication by NMR
Cdt1
MCM6
NMR Structure of Cdt1/Mcm6 Complex
NMR structure of Hox/Gem complex
Gem
DNA
Hox-HD
Hox-HD
Selected Publications
Zhou,B.,Liu,CD.,Xu,Z.,Zhu,G.*(2012)Structuralbasisforhomeodomainrecognitionbythecellcycle
regulatorGeminin,Proc. Natl. Acad. Sci. U S A. (in press)
Liu,CD.,Wu,RT.,Zhou,B.,Wang,J.,Wei,Z.,Tye,B.,Liang,C.,*Zhu,G.*(2012)StructuralInsightsintothe
Cdt1-MediatedMcm2-7 ChromatinLoading.Nucleic Acids Res.40,3208-17.
Chen,L.,Liu,CD.,Ko,F.,Xu,N.,Ng,I.,Yam,J.,*Zhu,G.*(2012)NovelbindingmodebetweenDLC1andthe
PTBdomainofTensin2:insightsintothemolecularmechanismoftumorsuppressionbyDLC1.J. Biol. Chem.
Wei,Z.,Liu,CD.,Zhou,B.,Xu,N.,Liang,C.,*Zhu,G.*(2010)Characterizationandstructuredeterminationof
theCdt1bindingdomainofhumanminichromosomemaintenance(Mcm)6.J. Biol. Chem. 285(17)12469-
73.
Hao,Z.,Tan,M.,Liu,CD.,Rui,F.,Wang,ED.*Zhu,G.*(2010)Studyingbasepairopen-closekineticsof
tRNALeubyTROSY-basedprotonexchangeNMRspectroscopy,FEBS Letter 584,4449-52.
Zhang,J.,Yu,L.,Wu,X.,Zou,L.,Sou,KL.,We,Z.,Cheng,X.,Zhu,G.*,Liang,C.*(2010)Theinteracting
domainsofhCdt1andhMcm6involvedinthechaomatingloadingoftheMcmcompleinhumancells.Cell
cycle9,24,7-6.
Zhou,B.,Chen,L.,Wu,X.,Wang,J.,Yin,Y.,Zhu,G.* (2008)MH1DomainofSMAD4BindsN-terminal
ResiduesoftheHomeodomainofHoxc9,BBA-Proteins&Proteomics 1784(5):747-52
Yin,Y.,Yu,VC.,Zhu,G.,*Chang,D*(2008)SET8playsaroleincontrollingG1/Stransitionbyblockinglysine
acetylationinhistonethroughbindingtoH4N-terminustail,Cell Cycle 7(10)1423-1432
Zhu,G.Yao,X.(2008)TROSY-basedNMRexperimentsforlargebiomolecules,Prog. in NMR
Spectroscopy.5249-68
Yin,Y.,Liu,CD.,Tsai,H.,Zhou,B.,Ngai,SM.,Zhu,G.*(2005)SET8RecognizestheSequence
RHRK20VLRDwithintheN-terminusofHistoneH4andMono-methylatesLysine20, J. Biol.
Chem.280,30025-31
Yao,Y.,Zhang,QS.,Yan,XZ.,Zhu,G.*,Wang,ED.*(2003)Substrate-InducedConformational
ChangesinEscherichia coli Arginyl-tRNASynthetaseObservedby19FNMRspectroscopy,FEBS
Letter 547 197-200
Smith,DK.,Radivojac,P.,Obradovic,Z.,Dunker,AK.,Zhu,G.(2003)ImprovedAminoAcid
FlexibilityParameters,Protein Science 12(5):1060-1072
ManD.,SzeKH.,SmithD.,WeiH.,Zhu,G*.IpN.(2003)SolutionStructureandBackbone
DynamicsoftheCarboxy-TerminalDomainoftheCytokineReceptorHomologyRegionof
CiliaryNeurotrophicFactorAlphaReceptor,J. Biol. Chem.278(26):23285-23294
Zhu,G.,Xia,Y.,Nicholson,L.,Sze,KH.,(2000)ProteindynamicsmeasurementsbyTROSY-
basedNMRexperiments.J. Magn. Reson.143,423-426.
Yan,XZ.,Xue,H.,Liu,Z.,Hang,J.,Wong,J.,Zhu,G.*(2000)NMRStudiesofBacillus subtilis
tRNATrpHyper-expressedinE.coli:AssignmentofIminoProtonSignalsandDeterminationof
ThermalStabilityJ. Biol.Chem.275,6712-6716
Development of bio-molecular NMR technology
Epigenetic regulation of cell cycle
NMR structure of DLC1/Tensin2-PTB complex
Cell proliferation
Cell differentiation
HBO1
SET8
SET8
CKII
P
Ub
SET8 is a cell cycle regulator
EX-TROSY:TROSYbasedNMRiminoprotonexchangeexperiment
A: Pulse sequence of EX-TROSY for 15N-labeled tRNA
leu
B: The 13C/15N filter used for double label tRNA
leu
and estimating NOEs
between carbons attached protons and imino proton
Thecorrelationbetween[Mg
2+
]dependentmillisecondconformationalflexibility
andaminoacylationofEctRNA
Leu
Blue: < 20%
Green: 20 - 40%
Red: > 40%
[Mg2+]/[tRNA] increased
from 1:1 to 15:1.
Aminoacylation of EctRNA
Leu
(CAG) increased as [Mg2+]/[tRNA]
increased from 1:1 to 15:1.