Research Interests

Our principal research interest is to investigate how biological macromolecules function as molecular machines by virtue of their structural design.

Structure biology of the RNA modification processes

Our goal is to understand the enzymatic processing of the anticodon domains of the tRNAs. tRNAs are most heavily modified amongst all the RNAs that contains about 100 known natural base modifications. Extensive modifications of the 34th (wobble base) and the 37th (3' to the anticodon) positions in several tRNAs play crucial role in accurate codon recognition and reading-frame maintenance. In addition, several modified anticodons contribute to genetic code plasticity. Wobble modification defects in mitochondrial tRNAs are implicated in several disease states. Given the central role of decoding event in the cellular physiology, very little is understood about the enzymatic targeting and processing of the tRNA anticodons. Therefore, we are studying the mechanism of these processes using crystallographic and other biophysical techniques. Of special interest to us are those eukaryotic enzymes that display multi-site specificity and perform intron-dependent tRNA modifications. Furthermore, we shall explore proteomic (mass-spectrometric) approaches to identify the complete set of anticodon processing enzymes in yeast.

Nano-scale artificial protein assembly design using a novel bio-mimetic approach.

Our goal is to explore a novel, bio-mimetic method to design and build nano-scale assemblies using functional protein modules as building blocks. Nano-biomaterial design is an emerging frontier of science that utilizes bio-molecules to manufacture devices with novel properties. However, precise positioning of molecules at nano-scale poses a challenge, which could be bypassed by imitating natural self-assembly processes. In order to understand the rules of the self-assembly in biological pathways, we are developing a bio-mimetic method to position a set of target protein modules in an ordered manner to form synthetic, supra-molecular assemblies. This project ties in with several frontiers of chemistry and biology, while taking advantage of the post-genomic information explosion in the area of protein sequence, structure and biological pathway databases. Success of our novel design approach will likely lead us to build artificial reaction-factories for industry and metabolic engineering purposes, biodegradable nano-vehicles for multiple drug delivery or in vivo drug synthesis in cancer therapeutics, protein arrays and other novel biomaterials.

Server for stop codon read-through prediction

http://www.doe-mbi.ucla.edu/~neel/RSA.php

Selected publications

A computational method to predict genetically encoded rare amino acids in proteins.
Chaudhuri BN, Yeates TO. Genome Biol. 2005;6(9):R79.

Crystal structure of the apo forms of 55 tRNA pseudouridine synthase from Mycobacterium tuberculosis: A hinge at the base of the catalytic cleft.
Chaudhuri BN, Chan S, Perry LJ, Yeates TO. J Biol Chem. 2004

The crystal structure of the first enzyme in the pantothenate biosynthetic pathway, ketopantoate hydroxymethyltransferase, from M tuberculosis.
Chaudhuri BN, Sawaya MR, Kim CY, Waldo GS, Park MS, Terwilliger TC, Yeates TO. Structure (Camb). 2003 Jul;11(7):753-64.

Toward understanding the mechanism of the complex cyclization reaction catalyzed by imidazole glycerolphosphate synthase: crystal structures of a ternary complex and the free enzyme.
Chaudhuri, BN, Lange, SC., Myers, RS., Chittur, SV., Davisson, VJ. & Smith, JL. Biochemistry. 2003, 42:7003-12

Crystal Structure of Imidazole Glycerol Phosphate Synthase: A Tunnel through a (b/a)8 Barrel Joins Two Active Sites.
Chaudhuri, BN, Lange, SC., Myers, RS., Chittur, SV., Davisson, VJ. & Smith, JL. Structure (Camb). 2001, 10, 987-97.