4XRR

Crystal structure of cals8 from micromonospora echinospora (P294S mutant)

「4WB1」から置き換えられました

4XRR の概要

• エントリーDOI: 10.2210/pdb4xrr/pdb
• 分子名称: CalS8, GLYCEROL (3 entities in total)
• 機能のキーワード: calicheamicin, oxidoreductase, structural genomics, psi-biology, midwest center for structural genomics, mcsg, enzyme discovery for natural product biosynthesis, natpro
• 由来する生物種: Micromonospora echinospora
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 96175.68

構造登録者

Michalska, K.,Bigelow, L.,Endres, M.,Babnigg, G.,Bingman, C.A.,Yennamalli, R.M.,Singh, S.,Kharel, M.K.,Thorson, J.S.,Phillips Jr., G.N.,Joachimiak, A.,Midwest Center for Structural Genomics (MCSG),Enzyme Discovery for Natural Product Biosynthesis (NatPro) (登録日: 2015-01-21, 公開日: 2015-02-11, 最終更新日: 2024-11-13)

主引用文献

Singh, S.,Michalska, K.,Bigelow, L.,Endres, M.,Kharel, M.K.,Babnigg, G.,Yennamalli, R.M.,Bingman, C.A.,Joachimiak, A.,Thorson, J.S.,Phillips, G.N.
Structural Characterization of CalS8, a TDP-alpha-D-Glucose Dehydrogenase Involved in Calicheamicin Aminodideoxypentose Biosynthesis.
J. Biol. Chem., 290:26249-26258, 2015

PubMed Abstract: Classical UDP-glucose 6-dehydrogenases (UGDHs; EC 1.1.1.22) catalyze the conversion of UDP-α-d-glucose (UDP-Glc) to the key metabolic precursor UDP-α-d-glucuronic acid (UDP-GlcA) and display specificity for UDP-Glc. The fundamental biochemical and structural study of the UGDH homolog CalS8 encoded by the calicheamicin biosynthetic gene is reported and represents one of the first studies of a UGDH homolog involved in secondary metabolism. The corresponding biochemical characterization of CalS8 reveals CalS8 as one of the first characterized base-permissive UGDH homologs with a >15-fold preference for TDP-Glc over UDP-Glc. The corresponding structure elucidations of apo-CalS8 and the CalS8·substrate·cofactor ternary complex (at 2.47 and 1.95 Å resolution, respectively) highlight a notably high degree of conservation between CalS8 and classical UGDHs where structural divergence within the intersubunit loop structure likely contributes to the CalS8 base permissivity. As such, this study begins to provide a putative blueprint for base specificity among sugar nucleotide-dependent dehydrogenases and, in conjunction with prior studies on the base specificity of the calicheamicin aminopentosyltransferase CalG4, provides growing support for the calicheamicin aminopentose pathway as a TDP-sugar-dependent process.

PubMed: 26240141
DOI: 10.1074/jbc.M115.673459

実験手法

X-RAY DIFFRACTION (2.55 Å)