Laboratory of thang chiu
Assistant Professor, PhD,
University of California, Los Angeles, 2001

Biography:
Dr. Chiu obtained his Bachelor of Science in Biochemistry and General Physics from the University of California, Los Angeles in 1992. He received his PhD in Biochemistry and Molecular Biology from the University of California, Los Angeles in 2001. From 2001 to 2007 he worked in the Lab of Molecular Biology at the National Institutes of Health, NIDDK.
From 2004 to 2007 he organized weekly research seminars among the X-ray crystallography groups. He is now an Assistant Professor for the Department of Biochemistry and Molecular Biology at Louisiana Health Sciences Center at New Orleans. His research interests are crystallographic and biochemical studies of proteins involved in HIV/AIDS, diabetes and innate immunity; protein folding, and the role of conformational changes on protein structure and function.

Research interests
Understanding the fundamental processes that govern protein folding, and the role of conformational dynamics in protein function, are vitally important for modern medicine, as protein misfolding and alternatively folded states can result in diseases, or provide new targets for therapeutic intervention. To pursue these studies we use modern molecular biology methods to design and produce recombinant proteins in bacterial or insect cells, purify them to homogeneity, and crystallize and determine their structures by X-ray crystallography. We corroborate our structural interpretations of the biological function by using site-directed mutagenesis to knock out or introduce interactions at critical active site or interface residues, and study the altered proteins crystallographically and biochemically.

To study the role of conformational dynamics in protein function, we are crystallizing and determining the structures of various prolyl peptidases, which have biological functions ranging from cancer to diabetes and psychological disorders. We do this by trapping each enzyme in different conformational states through crystallization, and determining their crystal structures (please check back in a few months for publications).

We also pursuing similar efforts to study key proteins involved in HIV/AIDS and innate immunity, which have potential benefits for millions of people worldwide.

A model of the active site (Frontiers in Medicinal Chemistry, (2006), vol. 3), based on the structures of Tn5 transposase with DNA and Bacillus Halodurans RNaseH with RNA/DNA hybrid. In this model of the active site in a 3' processing mode, one of the coordinated water molecule of the second metal cation (Mn2) is the nucleophile which attacks the phosphate group of G2, thereby breaking the O3' - P bond of A3 - G2. The configuration of the metal cations is adapted from both the previously cited Tn5 structure and the recent structure of B. halodurans RNase H bound to an RNA/DNA hybrid. In both studies, the first aspartate of the DDE motif chelates both metal cations. The placement of the DNA minor groove towards integrase is also based on these two studies, and is consistent with recent data which suggests that the DNA is oriented with the minor groove facing integrase: a minor groove benzo[a]pyrene diol epoxide deoxyguanine adduct at positions G(-4) and G(+5) have diminished 3' processing and strand transfer activities.

Selected Publications
J Kubelka, TK Chiu, DR Davies, WA Eaton, and J Hofrichter.  Sub-microsecond Protein Folding.  J.Mol. Biol., 2006, 359, 546-553.

TK Chiu and DR Davies.  Structure and Function of HIV-1 Integrase: An Update. Frontiers in Medicinal Chemistry, 2006, 3, 3-22.  Editors: Atta-ur-Rahman and Allen B. Reitz, Bentham Science Publishers LTD. (Book chapter)

U Baxa, N Cheng, DC Winkler, TK Chiu, DR Davies, D Sharma, H Inouye, DA Kirschner, RB Wickner, and AC Steven.  Filaments of the Ure2p Prion Protein have a Cross-b Core Structure. J. Structural Biology., 2005, 150, 170-179.
 
TK Chiu, J Kubelka, R Herbst-Irmer, WA Eaton, J Hofrichter, and DR Davies. High-resolution X-ray Crystal Structures of the Villin Headpiece Subdomain, an Ultrafast Folding Protein.  Proc. Nat. Acad. Sci., 2005, 102, 7517-7522.
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TK Chiu and DR Davies.  Structure and Function of HIV-1 Integrase. Current Topics in Medicinal Chemistry, 2004, 4, 965-979.
   
TK Chiu, C Sohn, RE Dickerson, and RC Johnson. Testing Water-mediated DNA Recognition by the Hin Recombinase. EMBO J., 2002, 21, 801-814.
  
DR Mack, TK Chiu and RE Dickerson. Intrinsic Bending and Deformability at the T-A Step of CCTTTAAAGG: A Comparative Analysis of T-A and A-T Steps within A-tracts.  J. Mol. Biol., 2001, 312, 1037-1049.
   
TK Chiu and RE Dickerson. 1Å Crystal Structures of B-DNA Reveal Sequence-Specific Binding and Groove-Specific Bending of DNA by Magnesium and Calcium. J. Mol. Biol., 2000, 301, 915-945.
   
TK Chiu, MK Grzeskowiak and RE Dickerson. Absence of Minor Groove Monovalent Cations in the Crosslinked Dodecamer CGCGAATTCGCG. J. Mol. Biol., 1999, 292, 589-608.

ML Kopka, GW Han, DS Goodsell, TK Chiu, WL Walker, JW Lown, and RE Dickerson. DNA Sequence Recognition in the Minor Groove by Polyamides, Using a GC-Specific Reading Element: A Perspective from Crystallography. Proceedings of the Tenth  Conversation, State University of New York, Albany, NY. 1998, 177-191.
  
RE Dickerson and TK Chiu. Helix Bending as a Role in Protein/DNA Recognition. Biopolymers: Nucleic Acid Sciences, 1997, 44, 361-403.
  
ML Kopka, DS Goodsell, GW Han, TK Chiu, JW Lown, and RE Dickerson. Defining GC-Specificity in the Minor Groove: Side-by-Side Binding of the Diimidazole Lexitropsin to CATGGCCATG.  Structure, 1997, 5, 1033-1046.
  
ZS Juo, TK Chiu, PM Leiberman, I Baikalov, AJ Berk, and RE Dickerson. How Proteins Recognize the TATA Box. J. Mol. Biol., 1996, 261, 239-254.