1YE6

Crystal structure of the Lys-274 to Arg mutant of Candida tenuis xylose reductase (AKR2B5) bound to NADP+

Summary for 1YE6

• Entry DOI: 10.2210/pdb1ye6/pdb
• Related: 1YE4
• Descriptor: NAD(P)H-dependent D-xylose reductase, SULFATE ION, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (5 entities in total)
• Functional Keywords: beta-alpha-barrel akr aldo-keto reductase coenzyme specificity nadp, oxidoreductase
• Biological source: Candida tenuis
• Total number of polymer chains: 4
• Total formula weight: 147943.02

Authors

Leitgeb, S.,Petschacher, B.,Wilson, D.K.,Nidetzky, B. (deposition date: 2004-12-28, release date: 2005-02-01, Last modification date: 2023-08-23)

Primary citation

Leitgeb, S.,Petschacher, B.,Wilson, D.K.,Nidetzky, B.
Fine tuning of coenzyme specificity in family 2 aldo-keto reductases revealed by crystal structures of the Lys-274-->Arg mutant of Candida tenuis xylose reductase (AKR2B5) bound to NAD(+) and NADP(+).
Febs Lett., 579:763-767, 2005

PubMed Abstract: Aldo-keto reductases of family 2 employ single site replacement Lys-->Arg to switch their cosubstrate preference from NADPH to NADH. X-ray crystal structures of Lys-274-->Arg mutant of Candida tenuis xylose reductase (AKR2B5) bound to NAD+ and NADP+ were determined at a resolution of 2.4 and 2.3A, respectively. Due to steric conflicts in the NADP+-bound form, the arginine side chain must rotate away from the position of the original lysine side chain, thereby disrupting a network of direct and water-mediated interactions between Glu-227, Lys-274 and the cofactor 2'-phosphate and 3'-hydroxy groups. Because anchoring contacts of its Glu-227 are lost, the coenzyme-enfolding loop that becomes ordered upon binding of NAD(P)+ in the wild-type remains partly disordered in the NADP+-bound mutant. The results delineate a catalytic reaction profile for the mutant in comparison to wild-type.

PubMed: 15670843
DOI: 10.1016/j.febslet.2004.12.063

Experimental method

X-RAY DIFFRACTION (2.3 Å)