PDBsum entry 4zhs

Oxidoreductase

PDB id: 4zhs

Contents

Protein chains

(+ 0 more) 356 a.a.

Ligands

SO4 ×6

Waters ×401

PDB id:

4zhs

Name:

Oxidoreductase

Title:

Crystal structure of aspartate semialdehyde dehydrogenase from trichophyton rubrum

Structure:

Aspartate semialdehyde dehydrogenase. Chain: d, c, b, e, a, f. Engineered: yes

Source:

Trichophyton rubrum bmu01672. Organism_taxid: 570842. Strain: bmu01672. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.60Å R-factor: 0.216 R-free: 0.257

Authors:

Q.Li,S.Cui

Key ref:

Q.Li et al. (2016). Structural Insights into the Tetrameric State of Aspartate-β-semialdehyde Dehydrogenases from Fungal Species. Sci Rep, 6, 21067. PubMed id: 26869335 DOI: 10.1038/srep21067

Date:

27-Apr-15 Release date: 02-Mar-16

Protein chains

A0A140UHG6  (A0A140UHG6_TRIRU) -  aspartate-semialdehyde dehydrogenase from Trichophyton rubrum BMU01672

Seq: 359 a.a.

Struc: 356 a.a.

Enzyme reactions

• Enzyme class: E.C.1.2.1.11 - aspartate-semialdehyde dehydrogenase.
• Pathway: Lysine biosynthesis (early stages)
• Reaction: L-aspartate 4-semialdehyde + phosphate + NADP⁺ = 4-phospho-L-aspartate + NADPH + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1038/srep21067

Sci Rep 6:21067 (2016)

PubMed id: 26869335

Structural Insights into the Tetrameric State of Aspartate-β-semialdehyde Dehydrogenases from Fungal Species.

Q.Li, Z.Mu, R.Zhao, G.Dahal, R.E.Viola, T.Liu, Q.Jin, S.Cui.

ABSTRACT

Aspartate-β-semialdehyde dehydrogenase (ASADH) catalyzes the second reaction in the aspartate pathway, a pathway required for the biosynthesis of one fifth of the essential amino acids in plants and microorganisms. Microarray analysis of a fungal pathogen T. rubrum responsible for most human dermatophytoses identified the upregulation of ASADH (trASADH) expression when the fungus is exposed to human skin, underscoring its potential as a drug target. Here we report the crystal structure of trASADH, revealing a tetrameric ASADH with a GAPDH-like fold. The tetramerization of trASADH was confirmed by sedimentation and SAXS experiments. Native PAGE demonstrated that this ASADH tetramerization is apparently universal in fungal species, unlike the functional dimer that is observed in all bacterial ASADHs. The helical subdomain in dimeric bacteria ASADH is replaced by the cover loop in archaeal/fungal ASADHs, presenting the determinant for this altered oligomerization. Mutations that disrupt the tetramerization of trASADH also abolish the catalytic activity, suggesting that the tetrameric state is required to produce the active fungal enzyme form. Our findings provide a basis to categorize ASADHs into dimeric and tetrameric enzymes, adopting a different orientation for NADP binding and offer a structural framework for designing drugs that can specifically target the fungal pathogens.