lys4 (SPBC1105.02c; UniProt Q9Y823) encodes homocitrate synthase (EC 2.3.3.14), the first and committed enzyme of the fungal alpha-aminoadipate pathway of lysine biosynthesis. It condenses acetyl-CoA with 2-oxoglutarate to homocitrate. Crystal structures of S. pombe HCS show a domain-swapped TIM-barrel homodimer. L-lysine competes directly with 2-oxoglutarate at the active site, which is the basis of feedback inhibition of the pathway. lys4 expression is induced by the homeobox protein Phx1; overexpressing lys4 suppresses the oxidative-stress-dependent lysine auxotrophy of CuZn-SOD-deficient cells, which reflects how sensitive the enzyme is to superoxide.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | MODIFY | Summary: Generic InterPro-derived parent of the specific activity, which is already annotated. Reason: Too general. Proposed replacements: homocitrate synthase activity Supporting Evidence: PMID:19776021 Here we report the crystal structure of the HCS apoenzyme from Schizosaccharomyces pombe and two distinct structures of the enzyme in complex with the substrate 2-oxoglutarate (2-OG). |
| GO:0004410 homocitrate synthase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference; consistent with structures and assays. Supporting Evidence: PMID:19776021 Here we report the crystal structure of the HCS apoenzyme from Schizosaccharomyces pombe and two distinct structures of the enzyme in complex with the substrate 2-oxoglutarate (2-OG). |
| GO:0004410 homocitrate synthase activity | IDA PMID:19776021 Crystal structure and functional analysis of homocitrate syn... | ACCEPT | Summary: Crystal structures of S. pombe HCS with 2-oxoglutarate, with functional analysis. Supporting Evidence: PMID:19776021 Here we report the crystal structure of the HCS apoenzyme from Schizosaccharomyces pombe and two distinct structures of the enzyme in complex with the substrate 2-oxoglutarate (2-OG). |
| GO:0004410 homocitrate synthase activity | IDA PMID:20089861 Structural basis for L-lysine feedback inhibition of homocit... | ACCEPT | Summary: Structure with L-lysine shows feedback inhibition by competition at the active site; in vitro HCS assays. Supporting Evidence: PMID:20089861 The structure illustrates that the amino acid directly competes with the substrate 2-oxoglutarate for binding within the active site of HCS. |
| GO:0004410 homocitrate synthase activity | IEA GO_REF:0000120 | ACCEPT | Summary: EC/RHEA mapping; consistent. Supporting Evidence: PMID:19776021 Here we report the crystal structure of the HCS apoenzyme from Schizosaccharomyces pombe and two distinct structures of the enzyme in complex with the substrate 2-oxoglutarate (2-OG). |
| GO:0004410 homocitrate synthase activity | IMP PMID:16299000 Inactivation of homocitrate synthase causes lysine auxotroph... | ACCEPT | Summary: lys4 overexpression raises HCS activity and suppresses the lysine requirement of sod1 cells. Supporting Evidence: PMID:16299000 overexpression of the lys4+ gene increased HCS enzyme activity and was sufficient to suppress the lysine requirement of the CuZn-SOD-deficient cells |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt location (mitochondrion); HCS is mitochondrial in fungi. Supporting Evidence: PMID:19776021 Here we report the crystal structure of the HCS apoenzyme from Schizosaccharomyces pombe and two distinct structures of the enzyme in complex with the substrate 2-oxoglutarate (2-OG). |
| GO:0005759 mitochondrial matrix | IC GO_REF:0000111 | KEEP AS NON CORE | Summary: Curator inference of matrix location from the activity. In S. cerevisiae, the HCS isozymes Lys20/Lys21 are largely nuclear. S. pombe Lys4 is annotated mitochondrial by UniProt, but its sub-organellar location has not been tested. Supporting Evidence: PMID:19776021 Here we report the crystal structure of the HCS apoenzyme from Schizosaccharomyces pombe and two distinct structures of the enzyme in complex with the substrate 2-oxoglutarate (2-OG). |
| GO:0009085 L-lysine biosynthetic process | EXP PMID:20089861 Structural basis for L-lysine feedback inhibition of homocit... | ACCEPT | Summary: Lysine feedback inhibition of HCS controls lysine biosynthesis in vivo. Supporting Evidence: PMID:20089861 The structure illustrates that the amino acid directly competes with the substrate 2-oxoglutarate for binding within the active site of HCS. |
| GO:0009085 L-lysine biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference; consistent. Supporting Evidence: PMID:19776021 Here we report the crystal structure of the HCS apoenzyme from Schizosaccharomyces pombe and two distinct structures of the enzyme in complex with the substrate 2-oxoglutarate (2-OG). |
| GO:0009085 L-lysine biosynthetic process | IDA PMID:19776021 Crystal structure and functional analysis of homocitrate syn... | ACCEPT | Summary: First committed step of lysine biosynthesis. Supporting Evidence: PMID:19776021 Here we report the crystal structure of the HCS apoenzyme from Schizosaccharomyces pombe and two distinct structures of the enzyme in complex with the substrate 2-oxoglutarate (2-OG). |
| GO:0009085 L-lysine biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: InterPro/ARBA mapping; consistent. Supporting Evidence: PMID:19776021 Here we report the crystal structure of the HCS apoenzyme from Schizosaccharomyces pombe and two distinct structures of the enzyme in complex with the substrate 2-oxoglutarate (2-OG). |
| GO:0009085 L-lysine biosynthetic process | IMP PMID:16299000 Inactivation of homocitrate synthase causes lysine auxotroph... | ACCEPT | Summary: lys4 controls the lysine requirement of sod1 cells. Supporting Evidence: PMID:16299000 overexpression of the lys4+ gene increased HCS enzyme activity and was sufficient to suppress the lysine requirement of the CuZn-SOD-deficient cells |
| GO:0009085 L-lysine biosynthetic process | IMP PMID:17622533 Six new amino acid-auxotrophic markers for targeted gene int... | ACCEPT | Summary: Auxotrophic marker screen. Supporting Evidence: PMID:17622533 Mutants that were auxotrophic for arginine, asparagine, cysteine, lysine, methionine and phenylalanine were isolated. |
| GO:0009085 L-lysine biosynthetic process | IMP PMID:3142867 Lysine biosynthesis pathway and biochemical blocks of lysine... | ACCEPT | Summary: Classical lysine auxotroph (lys4-95) blocked before aminoadipate. Supporting Evidence: PMID:3142867 Of the eight enzyme activities of the AA pathway that have been examined so far, six were present in the extract of wild-type S. pombe cells. |
| GO:0046912 acyltransferase activity, acyl groups converted into alkyl on transfer | IEA GO_REF:0000002 | MODIFY | Summary: Generic InterPro-derived parent of the specific activity, which is already annotated. Reason: Too general. Proposed replacements: homocitrate synthase activity Supporting Evidence: PMID:19776021 Here we report the crystal structure of the HCS apoenzyme from Schizosaccharomyces pombe and two distinct structures of the enzyme in complex with the substrate 2-oxoglutarate (2-OG). |
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