Structure of porcine aldehyde reductase holoenzyme

Abstract

Aldehyde reductase, a member of the aldo-keto reductase superfamily, catalyzes the NADPH-dependent reduction of a variety of aldehydes to their corresponding alcohols. The structure of porcine aldehyde reductase-NADPH binary complex has been determined by x-ray diffraction methods and refined to a crystallographic R-factor of 0.20 at 2.4 A resolution. The tertiary structure of aldehyde reductase is similar to that of aldose reductase and consists of an alpha/beta-barrel with the active site located at the carboxy terminus of the strands of the barrel. Unlike aldose reductase, the N epsilon 2 of the imidazole ring of His 113 in aldehyde reductase interacts, through a hydrogen bond, with the amide group of the nicotinamide ring of NADPH.

Kvβ Subunit Oxidoreductase Activity and Kv1 Potassium Channel Trafficking

“…These and other studies of AKRs (45,46) have shown that the tyrosine hydroxyl group, whose pK a is perturbed through association with a neighboring lysine and aspartate, acts as the proton donor during the protonation of the carbonyl oxygen group of the substrate. Thus, eliminating the critical side chain hydroxyl group in the Kv␤2 Y90F and Kv␤1.1 Y124F mutants, although retaining the overall hydrophobicity and size of the residue, should eliminate catalysis in Kv␤s as it does in other AKRs.…”

The Aldo-Keto Reductase Superfamily and its Role in Drug Metabolism and Detoxification

“…Binding of NADPH to the protein is similar to other AKRs (e.g., AKR1B1) in that cofactor binds in the extended conformation across the lip of the barrel, although affinity is slightly lower: the K d NADPH of AKR1A1 is 13-fold higher than that of AKR1B1, i.e., 130 (Barski et al, 1995) versus 10 (Ehrig et al, 1994 nM. Also, in contrast to AKR1B proteins, AKR1A1 lacks the hyper-reactive active site cysteine and the Nε of the imidazole ring of the active site histidine (His-112) interacts with the amide side chain of the nicotinamide ring of NADPH (el-Kabbani et al, 1995), underscoring differences between AKRs in the exact positioning of NADPH in the active site.…”

“…The enzyme is ubiquitously expressed in most tissues with highest levels in the kidney proximal tubules (Barski et al, 2005;Barski et al, 1999). The crystal structure of AKR1A1 reveals a canonical AKR β-barrel with the active site located at the C-terminus (el-Kabbani et al, 1995). Binding of NADPH to the protein is similar to other AKRs (e.g., AKR1B1) in that cofactor binds in the extended conformation across the lip of the barrel, although affinity is slightly lower: the K d NADPH of AKR1A1 is 13-fold higher than that of AKR1B1, i.e., 130 (Barski et al, 1995) versus 10 (Ehrig et al, 1994 nM.…”

Some peculiarities in the manifestation of oxidative stress and current status of antioxidant system in adolescents of different age groups with obesity, complicated by insulin resistance and without it

“…В связи с этим оксидативный стресс выступает в роли одного из важных неспецифических патогенетических звеньев формирования метаболических нарушений при нейроэндокринном ожирении. Важную роль в адаптации к повреждающему действию оксидативного стресса приобретает ферментативная система утилизации эндогенных альдегидов [9,10], которая включает в себя ферменты, катализирующие окислительно-восстановительные превращения альдегидов, а также их конъюгацию с глутатионом [11,12]. Однако изучению её состояния при ожирении до настоящего времени не уделялось должного внимания.…”