5V7G

Crystal structure of NADPH-dependent glyoxylate/hydroxypyruvate reductase SMc04462 (SmGhrB) from Sinorhizobium meliloti in complex with NADPH and oxalate

5V7G の概要

• エントリーDOI: 10.2210/pdb5v7g/pdb
• 関連するPDBエントリー: 5J23 5UOG 5V6Q 5V72 5V7N
• 分子名称: NADPH-dependent glyoxylate/hydroxypyruvate reductase, OXALATE ION, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (7 entities in total)
• 機能のキーワード: nadph-dependent glyoxylate/hydroxypyruvate reductase, nadp, nysgrc, sinorhizobium meliloti, structural genomics, psi-biology, new york structural genomics research consortium, oxidoreductase
• 由来する生物種: Rhizobium meliloti (strain 1021) (Ensifer meliloti)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 141277.80

構造登録者

Shabalin, I.G.,Mason, D.V.,Handing, K.B.,Kutner, J.,Matelska, D.,Cooper, D.R.,Bonanno, J.,Almo, S.C.,Minor, W.,New York Structural Genomics Research Consortium (NYSGRC) (登録日: 2017-03-20, 公開日: 2017-03-29, 最終更新日: 2023-10-04)

主引用文献

Kutner, J.,Shabalin, I.G.,Matelska, D.,Handing, K.B.,Gasiorowska, O.,Sroka, P.,Gorna, M.W.,Ginalski, K.,Wozniak, K.,Minor, W.
Structural, Biochemical, and Evolutionary Characterizations of Glyoxylate/Hydroxypyruvate Reductases Show Their Division into Two Distinct Subfamilies.
Biochemistry, 57:963-977, 2018

PubMed Abstract: The d-2-hydroxyacid dehydrogenase (2HADH) family illustrates a complex evolutionary history with multiple lateral gene transfers and gene duplications and losses. As a result, the exact functional annotation of individual members can be extrapolated to a very limited extent. Here, we revise the previous simplified view on the classification of the 2HADH family; specifically, we show that the previously delineated glyoxylate/hydroxypyruvate reductase (GHPR) subfamily consists of two evolutionary separated GHRA and GHRB subfamilies. We compare two representatives of these subfamilies from Sinorhizobium meliloti (SmGhrA and SmGhrB), employing a combination of biochemical, structural, and bioinformatics approaches. Our kinetic results show that both enzymes reduce several 2-ketocarboxylic acids with overlapping, but not equivalent, substrate preferences. SmGhrA and SmGhrB show highest activity with glyoxylate and hydroxypyruvate, respectively; in addition, only SmGhrB reduces 2-keto-d-gluconate, and only SmGhrA reduces pyruvate (with low efficiency). We present nine crystal structures of both enzymes in apo forms and in complexes with cofactors and substrates/substrate analogues. In particular, we determined a crystal structure of SmGhrB with 2-keto-d-gluconate, which is the biggest substrate cocrystallized with a 2HADH member. The structures reveal significant differences between SmGhrA and SmGhrB, both in the overall structure and within the substrate-binding pocket, offering insight into the molecular basis for the observed substrate preferences and subfamily differences. In addition, we provide an overview of all GHRA and GHRB structures complexed with a ligand in the active site.

PubMed: 29309127
DOI: 10.1021/acs.biochem.7b01137

実験手法

X-RAY DIFFRACTION (1.75 Å)