NCGR_LOCUS29329 - Bifunctional Aspartate Kinase / Homoserine Dehydrogenase

Gene Summary

• UniProt ID: A0A811PKG6 (TrEMBL, unreviewed)
• Organism: Miscanthus lutarioriparius (taxon 422564, Poaceae/grasses)
• Protein: Bifunctional aspartokinase/homoserine dehydrogenase (AK-HSD)
• Size: 920 amino acids
• Domains: N-terminal aspartate kinase (AA_kinase, Pfam PF00696), C-terminal homoserine dehydrogenase (Homoserine_dh, PF00742), NAD-binding domain (NAD_binding_3, PF03447), two ACT regulatory domains (positions 416-491 and 497-574)
• EC numbers: EC 2.7.2.4 (aspartate kinase), EC 1.1.1.3 (homoserine dehydrogenase)
• Localization: Chloroplast/plastid

Functional Context

Bifunctional AK-HSD enzymes catalyze the first (AK) and third (HSD) steps in the aspartate-derived amino acid biosynthetic pathway, which produces lysine, threonine, and methionine from L-aspartate. This is a conserved pathway in plants and bacteria.

Reactions catalyzed:

1. Aspartate kinase (EC 2.7.2.4): L-aspartate + ATP -> 4-phospho-L-aspartate + ADP
2. Homoserine dehydrogenase (EC 1.1.1.3): L-aspartate 4-semialdehyde + NAD(P)H + H+ -> L-homoserine + NAD(P)+

Pathway involvement:

• L-lysine biosynthesis via DAP pathway (step 1)
• L-threonine biosynthesis (steps 1 and 3)
• L-methionine biosynthesis via de novo pathway (steps 1 and 3)
• L-homoserine biosynthesis (catalyzes the HSD step directly)

Plant AK-HSD Biology

In plants like Arabidopsis, bifunctional AK-HSD enzymes (AK-HSDH I and II) are well-characterized PMID:26175505. Key features:

• All aspartate pathway steps (except final methionine methylation) occur in the chloroplast
• AK-HSD enzymes are subject to feedback inhibition by threonine via ACT domains
• The ACT domains serve as allosteric regulatory sensors for threonine
• Plants typically have both monofunctional AK (lysine-sensitive) and bifunctional AK-HSD (threonine-sensitive) forms

Genome Context

The M. lutarioriparius genome was assembled at chromosome scale (2.07 Gb, 57,710 genes) PMID:33911077. This is a C4 grass used as a biomass energy crop. The NCGR_LOCUS29329 sequence is from WGS preliminary data.

Notes on Annotation Quality

• All 11 existing GO annotations are IEA (electronic) - no experimental evidence
• The protein is unreviewed (TrEMBL) and from WGS preliminary data
• Domain architecture is highly consistent with bifunctional AK-HSD: the InterPro signatures (IPR001341, IPR018042, IPR011147, IPR001342, IPR005106) are all diagnostic
• PANTHER classification (PTHR43070:SF5) confirms homoserine dehydrogenase subfamily
• CDD domain cd04257 (AAK_AK-HSDH) is specific to the bifunctional enzyme