4XB1

Hyperthermophilic archaeal homoserine dehydrogenase in complex with NADPH

Summary for 4XB1

• Entry DOI: 10.2210/pdb4xb1/pdb
• Related: 4XB2
• Descriptor: 319aa long hypothetical homoserine dehydrogenase, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, SODIUM ION, ... (5 entities in total)
• Functional Keywords: rossmann fold, oxidoreductase
• Biological source: Pyrococcus horikoshii OT3
• Total number of polymer chains: 2
• Total formula weight: 76077.68

Authors

Sakuraba, H.,Inoue, S.,Yoneda, K.,Ohshima, T. (deposition date: 2014-12-16, release date: 2015-07-15, Last modification date: 2023-11-08)

Primary citation

Hayashi, J.,Inoue, S.,Kim, K.,Yoneda, K.,Kawarabayasi, Y.,Ohshima, T.,Sakuraba, H.
Crystal Structures of a Hyperthermophilic Archaeal Homoserine Dehydrogenase Suggest a Novel Cofactor Binding Mode for Oxidoreductases.
Sci Rep, 5:11674-11674, 2015

PubMed Abstract: NAD(P)-dependent dehydrogenases differ according to their coenzyme preference: some prefer NAD, others NADP, and still others exhibit dual cofactor specificity. The structure of a newly identified archaeal homoserine dehydrogenase showed this enzyme to have a strong preference for NADP. However, NADP did not act as a cofactor with this enzyme, but as a strong inhibitor of NAD-dependent homoserine oxidation. Structural analysis and site-directed mutagenesis showed that the large number of interactions between the cofactor and the enzyme are responsible for the lack of reactivity of the enzyme towards NADP. This observation suggests this enzyme exhibits a new variation on cofactor binding to a dehydrogenase: very strong NADP binding that acts as an obstacle to NAD(P)-dependent dehydrogenase catalytic activity.

PubMed: 26154028
DOI: 10.1038/srep11674

Experimental method

X-RAY DIFFRACTION (2.3 Å)