6qap

Structure of the human aldehyde dehydrogenase 9A1 in C2 space groupStructure of the human aldehyde dehydrogenase 9A1 in C2 space group

Structural highlights 6qap is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.3Å Ligands: , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function AL9A1_HUMAN Converts gamma-trimethylaminobutyraldehyde into gamma-butyrobetaine. Catalyzes the irreversible oxidation of a broad range of aldehydes to the corresponding acids in an NAD-dependent reaction. Publication Abstract from PubMed Aldehyde dehydrogenases (ALDHs) constitute a superfamily of NAD(P)(+)-dependent enzymes, which detoxify aldehydes produced in various metabolic pathways to the corresponding carboxylic acids. Among the 19 human ALDHs, the cytosolic ALDH9A1 has so far never been fully enzymatically characterized and its structure is still unknown. Here, we report complete molecular and kinetic properties of human ALDH9A1 as well as three crystal forms at 2.3 A, 2.9 A and 2.5 A resolution. We show that ALDH9A1 exhibits wide substrate specificity to aminoaldehydes, aliphatic and aromatic aldehydes with a clear preference for gamma -trimethylaminobutyraldehyde (TMABAL). The structure of ALDH9A1 reveals that the enzyme assembles as a tetramer. Each ALDH monomer displays a typical ALDHs fold composed of an oligomerization domain, a coenzyme domain, a catalytic domain and an inter-domain linker highly conserved in amino-acid sequence and folding. Nonetheless, structural comparison reveals a position and a fold of the inter-domain linker of ALDH9A1 never observed in any other ALDH so far. This unique difference is not compatible with the presence of a bound substrate and a large conformational rearrangement of the linker up to 30 A has to occur to allow the access of the substrate channel. Moreover, the alphabetaE region consisting of an alpha-helix and a beta-strand of the coenzyme domain at the dimer interface are disordered, likely due to the loss of interactions with the inter-domain linker, which leads to incomplete NAD(+) binding pocket. Kinetic and structural analysis of human ALDH9A1.,Koncitikova R, Vigouroux A, Kopecna M, Sebela M, Morera S, Kopecny D Biosci Rep. 2019 Mar 26. pii: BSR20190558. doi: 10.1042/BSR20190558. PMID:30914451 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aldehyde dehydrogenase 3D structures

spinqualitylabelsall models 6qap, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image