1EKO

PIG ALDOSE REDUCTASE COMPLEXED WITH IDD384 INHIBITOR

Summary for 1EKO

• Entry DOI: 10.2210/pdb1eko/pdb
• Related: 1EL3
• Descriptor: ALDOSE REDUCTASE, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, [2,6-DIMETHYL-4-(2-O-TOLYL-ACETYLAMINO)-BENZENESULFONYL]-GLYCINE, ... (4 entities in total)
• Functional Keywords: aldose reductase, inhibition, diabetes, oxidoreductase
• Biological source: Sus scrofa (pig)
• Cellular location: Cytoplasm: P80276
• Total number of polymer chains: 1
• Total formula weight: 36957.89

Authors

Podjarny, A. (deposition date: 2000-03-09, release date: 2000-05-10, Last modification date: 2024-04-03)

Primary citation

Calderone, V.,Chevrier, B.,Van Zandt, M.,Lamour, V.,Howard, E.,Poterszman, A.,Barth, P.,Mitschler, A.,Lu, J.,Dvornik, D.M.,Klebe, G.,Kraemer, O.,Moorman, A.R.,Moras, D.,Podjarny, A.
The structure of human aldose reductase bound to the inhibitor IDD384.
Acta Crystallogr.,Sect.D, 56:536-540, 2000

PubMed Abstract: The crystallographic structure of the complex between human aldose reductase (AR2) and one of its inhibitors, IDD384, has been solved at 1.7 A resolution from crystals obtained at pH 5.0. This structure shows that the binding of the inhibitor's hydrophilic head to the catalytic residues Tyr48 and His110 differs from that found previously with porcine AR2. The difference is attributed to a change in the protonation state of the inhibitor (pK(a) = 4.52) when soaked with crystals of human (at pH 5.0) or pig lens AR2 (at pH 6.2). This work demonstrates how strongly the detailed binding of the inhibitor's polar head depends on its protonation state.

PubMed: 10771421
DOI: 10.1107/S0907444900002341

Experimental method

X-RAY DIFFRACTION (2.2 Å)