Utilizing NMR to study the structure of growth-inhibitory proteins.

Abstract

The underlying premise of structural biology is that the fundamental understanding of biological functions lies in the three-dimensional structures of proteins and other biopolymers. The two well-established experimental methods for determining the high-resolution structures of proteins have both contributed to the wealth of structural information available for the tumor suppressor genes. The tumor suppressor proteins whose structures have been determined by nuclear magnetic resonance (NMR) spectroscopy are listed in Table 1. Although X-ray crystallography plays a central role in high-throughput structure determination in the current structural genomics efforts, several features of NMR spectroscopy make it extremely well suited for three-dimensional structure determination as well as for the structure-function analysis of proteins (,). Table 1 Tumor Suppressor Proteins Whose Structures Have Been Determined by NMR Spectroscopy in Solution, with Protein Data Bank Identification (PDB ID) Codes (http://www.rcsb.org/pdb/) Tumor suppressor structures determined by NMR spectroscopy PDB ID Refined solution structure of the oligomerization domain of the tumour suppressor p53 (39,40) 1SAE, 1SAF, 1SAG, 1SAH, 1SAI, 1SAJ, 1SAK, 1SAL Solution structure determination of a p53 mutant dimerization domain (44) 1AU1 NMR solution structure of designed p53 dimer (63) 1HS5 Solution structure of a conserved C-terminal domain of p73 with structural homology to the Sam domain (64) 1COK Solution structure of P18-Ink4C, 21 structures (56) 1BU9 Tumor suppressor P16Ink4A: determination of solution structure and analyses of its interaction with cyclin-dependent kinase 4 (58) 1A5E, 2A5E Solution NMR structure of tumor suppressor P16Ink4A (59) 1DC2 Tumor suppressor P15(Ink4B) structure by comparative modeling and NMR data (59) 1D9S High-resolution solution structure of human pNR-2/pS2: a single trefoil motif protein (65) 1PS2 NMR solution structure of the disulfide-linked homo-dimer of human Tff1 (66) 1HI7