Zarembinski T I, Hung L W, Mueller-Dieckmann H J, Kim K K, Yokota H, Kim R, Kim S H
Physical Biosciences Division of Lawrence Berkeley National Laboratory, University of California, Berkeley, CA 94720, USA.
Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15189-93. doi: 10.1073/pnas.95.26.15189.
Many small bacterial, archaebacterial, and eukaryotic genomes have been sequenced, and the larger eukaryotic genomes are predicted to be completely sequenced within the next decade. In all genomes sequenced to date, a large portion of these organisms' predicted protein coding regions encode polypeptides of unknown biochemical, biophysical, and/or cellular functions. Three-dimensional structures of these proteins may suggest biochemical or biophysical functions. Here we report the crystal structure of one such protein, MJ0577, from a hyperthermophile, Methanococcus jannaschii, at 1.7-A resolution. The structure contains a bound ATP, suggesting MJ0577 is an ATPase or an ATP-mediated molecular switch, which we confirm by biochemical experiments. Furthermore, the structure reveals different ATP binding motifs that are shared among many homologous hypothetical proteins in this family. This result indicates that structure-based assignment of molecular function is a viable approach for the large-scale biochemical assignment of proteins and for discovering new motifs, a basic premise of structural genomics.
许多细菌、古细菌和真核生物的小基因组已被测序，预计在未来十年内更大的真核生物基因组也将被完全测序。在迄今为止测序的所有基因组中，这些生物预测的蛋白质编码区域中有很大一部分编码了生化、生物物理和/或细胞功能未知的多肽。这些蛋白质的三维结构可能暗示其生化或生物物理功能。在此，我们报告了一种来自嗜热古菌詹氏甲烷球菌的此类蛋白质MJ0577的晶体结构，分辨率为1.7埃。该结构包含一个结合的ATP，表明MJ0577是一种ATP酶或ATP介导的分子开关，我们通过生化实验证实了这一点。此外，该结构揭示了该家族中许多同源假设蛋白质共有的不同ATP结合基序。这一结果表明，基于结构的分子功能分配是对蛋白质进行大规模生化分配以及发现新基序的可行方法，这是结构基因组学的一个基本前提。
