Structure of Archaeal Alanine Dehydrogenase and Relation to Bacterial and Human Proteins

Published

October 16, 2008

Author(s)

David Travis Gallagher, H G. Monbouquette, I Schroeder, Hugh Robinson, Marcia J. Holden, N Smith

Abstract

In the hyperthermophilic archaeon Archaeoglobus fulgidus, gene AF1665 encodes an L-ala dehydrogenase (AlaDH, EC 1.4.1.1) but has been annotated as an ornithine cyclodeaminase (OCD) based on homology with the mu crystalline/ornithine cyclodeaminase protein family. We report the structure of the AF1665 AlaDH at 2.3 in a C2 crystal form with the 70 kDa dimer in the asymmetric unit. Consistent with its lack of homology to bacterial AlaDH proteins which are mostly hexameric, the archael AlaDH has a unique structure. Although both sets of AlaDH enzymes have a Rossmann-type NAD-binding domain, the arrangement of its strand elements is different, and the other (catalytic) domain in the archaeal protein has a new fold. The overall structure and active site are compared with other dehydrogenases including the AlaDH from Phormidium lapideum. The AF1665 AlaDH structure represents an ancient and previously undescribed subclass of Rossmann-fold proteins that also includes bacterial OCD and mammalian mu crystallins. In human, thyroid hormone binding protein belongs to the same family, with 30% sequence identity to AF1665.

Citation

Nature Structural Biology

Pub Type

Journals

Keywords

anisotropic refinement, crystal structure, parahydroxybenzoate, ultrahigh resolution, x-ray diffraction

Citation

Gallagher, D. , Monbouquette, H. , Schroeder, I. , Robinson, H. , Holden, M. and Smith, N. (2008), Structure of Archaeal Alanine Dehydrogenase and Relation to Bacterial and Human Proteins, Nature Structural Biology (Accessed January 17, 2025)