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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. 2005 Jan 31; 579(3):763-7.FL

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.

Authors+Show Affiliations

Institute of Biotechnology and Biochemical Engineering, Graz University of Technology, Petersgasse 12/I, A-8010 Graz, Austria.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15670843

Citation

Leitgeb, Stefan, et al. "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 Letters, vol. 579, no. 3, 2005, pp. 763-7.
Leitgeb S, Petschacher B, Wilson DK, et al. 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. 2005;579(3):763-7.
Leitgeb, S., Petschacher, B., Wilson, D. K., & Nidetzky, B. (2005). 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 Letters, 579(3), 763-7.
Leitgeb S, et al. 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. 2005 Jan 31;579(3):763-7. PubMed PMID: 15670843.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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+. AU - Leitgeb,Stefan, AU - Petschacher,Barbara, AU - Wilson,David K, AU - Nidetzky,Bernd, PY - 2004/11/05/received PY - 2004/12/10/revised PY - 2004/12/15/accepted PY - 2005/1/27/pubmed PY - 2005/4/14/medline PY - 2005/1/27/entrez SP - 763 EP - 7 JF - FEBS letters JO - FEBS Lett. VL - 579 IS - 3 N2 - 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. SN - 0014-5793 UR - https://www.unboundmedicine.com/medline/citation/15670843/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+_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-5793(05)00020-7 DB - PRIME DP - Unbound Medicine ER -