Lubkowski Jacek, Dauter Miroslawa, Aghaiypour Khosrow, Wlodawer Alexander, Dauter Zbigniew
Macromolecular Crystallography Laboratory, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
Acta Crystallogr D Biol Crystallogr. 2003 Jan;59(Pt 1):84-92. doi: 10.1107/s0907444902019443. Epub 2002 Dec 19.
An X-ray structure of L-asparaginase from Erwinia chrysanthemi (ErA) has been refined at 1 A resolution to an R factor of below 0.1, using data collected on a synchrotron source. With four molecules of the enzyme consisting of 327 amino acids each, this crystal contains one of the largest asymmetric units of a protein refined to date at atomic resolution. Previously, structures of ErA and of related enzymes from other bacterial sources have been refined at resolutions not exceeding 1.7 A; thus, the present structure represents a very significant improvement in the quality of the available models of these proteins and should provide a good basis for future studies of the conformational variability of proteins, identification of subtle conformational features and corroboration of the stereochemical libraries, amongst other things. L-Asparaginases, which are enzymes that catalyze the hydrolysis of L-asparagine to aspartic acid, have been used for over 30 y as therapeutic agents in the treatment of acute childhood lymphoblastic leukemia, although the details of the enzymatic reaction and substrate specificity have not yet been completely elucidated. This atomic resolution structure is a step in that direction.
利用在同步辐射源上收集的数据，菊花欧文氏菌（ErA）L-天冬酰胺酶的X射线结构已在1埃分辨率下精修至R因子低于0.1。该晶体含有四个分子的这种酶，每个分子由327个氨基酸组成，是迄今为止在原子分辨率下精修的蛋白质最大不对称单元之一。此前，ErA以及其他细菌来源的相关酶的结构已在不超过1.7埃的分辨率下精修；因此，目前的结构代表了这些蛋白质现有模型质量的显著提高，应为未来关于蛋白质构象变异性研究、细微构象特征识别以及立体化学文库确证等提供良好基础。L-天冬酰胺酶是催化L-天冬酰胺水解成天冬氨酸的酶，尽管酶促反应和底物特异性的细节尚未完全阐明，但已作为治疗药物用于治疗儿童急性淋巴细胞白血病30多年了。这种原子分辨率结构是朝着这个方向迈出的一步。
