Crystal structures and kinetic studies of a laboratory evolved aldehyde reductase explain the dramatic shift of its new substrate specificity

Sridhar, S.; Zavarise, A.; Kiema, T.-R.; Dalwani, S.; Eriksson, T.; Hajee, Y.; Reddy Enugala, T.; Wierenga, R.K.; Widersten, M.

doi:10.1107/S205225252300444X

Figure 7
The modes of binding of NADH and NAD⁺ in the FucO catalytic site are the same. The superimposed structures are of the DA1472 variant (magenta, PDB entry 7qnh) with bound NADH and of the D47 variant (light-green, PDB entry 7r0p) with bound NAD⁺. Both active sites are also complexed with Fe²⁺. Also included are the superimposed wild-type catalytic site of the 5br4 structure (blue, with bound NAD⁺ and Zn²⁺) and the superimposed active site of the 7qnf structure of the DA1472 variant (yellow), with the bound ethyleneglycol (EDO, cyan), ADPR and Fe²⁺. The Zn²⁺ position (as captured in the 5br4 structure) is shifted by approximately 1 Å, away from the canonical Fe²⁺ position. The interactions of the Zn²⁺ ion with the side-chain atoms of Asp196, His200, His263 and His277 in the 5br4 structure, and the interaction of the Fe²⁺ ion with EDO in the 7qnf structure, are highlighted by dotted lines. The hydrogen bond between the amide nitrogen of the nicotinamide moiety of NAD⁺ and NADH and the peptide oxygen of residue 151 is also highlighted by a dotted line.

IUCrJ

Volume 10| Part 4| July 2023| Pages 437-447

ISSN: 2052-2525

https://doi.org/10.1107/S205225252300444X

BIOLOGY | MEDICINE

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