4P53

ValA (2-epi-5-epi-valiolone synthase) from Streptomyces hygroscopicus subsp. jinggangensis 5008 with NAD+ and Zn2+ bound

4P53 の概要

• エントリーDOI: 10.2210/pdb4p53/pdb
• 分子名称: Cyclase, ZINC ION, 1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE, ... (5 entities in total)
• 機能のキーワード: lyase, sugar phosphate cyclase, pseudoglycoside, sedoheptulose 7-phosphate
• 由来する生物種: Streptomyces hygroscopicus subsp. jinggangensis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 46740.67

構造登録者

Kean, K.M.,Codding, S.J.,Karplus, P.A. (登録日: 2014-03-13, 公開日: 2014-07-30, 最終更新日: 2023-09-27)

主引用文献

Kean, K.M.,Codding, S.J.,Asamizu, S.,Mahmud, T.,Karplus, P.A.
Structure of a sedoheptulose 7-phosphate cyclase: ValA from Streptomyces hygroscopicus.
Biochemistry, 53:4250-4260, 2014

PubMed Abstract: Sedoheptulose 7-phosphate cyclases (SH7PCs) encompass three enzymes involved in producing the core cyclitol structures of pseudoglycosides and similar bioactive natural products. One such enzyme is ValA from Streptomyces hygroscopicus subsp. jinggangensis 5008, which makes 2-epi-5-epi-valiolone as part of the biosynthesis of the agricultural antifungal agent validamycin A. We present, as the first SH7PC structure, the 2.1 Å resolution crystal structure of ValA in complex with NAD+ and Zn2+ cofactors. ValA has a fold and active site organization resembling those of the sugar phosphate cyclase dehydroquinate synthase (DHQS) and contains two notable, previously unrecognized interactions between NAD+ and Asp side chains conserved in all sugar phosphate cyclases that may influence catalysis. Because the domains of ValA adopt a nearly closed conformation even though no sugar substrate is present, comparisons with a ligand-bound DHQS provide a model for aspects of substrate binding. One striking active site difference is a loop that adopts a distinct conformation as a result of an Asp→Asn change with respect to DHQS and alters the identity and orientation of a key Arg residue. This and other active site differences in ValA are mostly localized to areas where the ValA substrate differs from that of DHQS. Sequence comparisons with a second SH7PC making a product with distinct stereochemistry lead us to postulate that the product stereochemistry of a given SH7PC is not the result of events taking place during catalysis but is accomplished by selective binding of either the α or β pyranose anomer of the substrate.

PubMed: 24832673
DOI: 10.1021/bi5003508

実験手法

X-RAY DIFFRACTION (2.1 Å)