ID Q8DQ00_STRR6 Unreviewed; 358 AA. AC Q8DQ00; DT 01-MAR-2003, integrated into UniProtKB/TrEMBL. DT 01-MAR-2003, sequence version 1. DT 08-NOV-2023, entry version 129. DE RecName: Full=Aspartate-semialdehyde dehydrogenase {ECO:0000256|ARBA:ARBA00013120, ECO:0000256|HAMAP-Rule:MF_02121}; DE Short=ASA dehydrogenase {ECO:0000256|HAMAP-Rule:MF_02121}; DE Short=ASADH {ECO:0000256|HAMAP-Rule:MF_02121}; DE EC=1.2.1.11 {ECO:0000256|ARBA:ARBA00013120, ECO:0000256|HAMAP-Rule:MF_02121}; DE AltName: Full=Aspartate-beta-semialdehyde dehydrogenase {ECO:0000256|HAMAP-Rule:MF_02121}; GN Name=asd {ECO:0000256|HAMAP-Rule:MF_02121, GN ECO:0000313|EMBL:AAK99722.1}; GN OrderedLocusNames=spr0918 {ECO:0000313|EMBL:AAK99722.1}; OS Streptococcus pneumoniae (strain ATCC BAA-255 / R6). OC Bacteria; Bacillota; Bacilli; Lactobacillales; Streptococcaceae; OC Streptococcus. OX NCBI_TaxID=171101 {ECO:0000313|EMBL:AAK99722.1, ECO:0000313|Proteomes:UP000000586}; RN [1] {ECO:0000313|EMBL:AAK99722.1, ECO:0000313|Proteomes:UP000000586} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC BAA-255 / R6 {ECO:0000313|Proteomes:UP000000586}; RX PubMed=11544234; DOI=10.1128/JB.183.19.5709-5717.2001; RA Hoskins J.A., Alborn W.Jr., Arnold J., Blaszczak L., Burgett S., RA DeHoff B.S., Estrem S., Fritz L., Fu D.-J., Fuller W., Geringer C., RA Gilmour R., Glass J.S., Khoja H., Kraft A., LaGace R., LeBlanc D.J., RA Lee L.N., Lefkowitz E.J., Lu J., Matsushima P., McAhren S., McHenney M., RA McLeaster K., Mundy C., Nicas T.I., Norris F.H., O'Gara M., Peery R., RA Robertson G.T., Rockey P., Sun P.-M., Winkler M.E., Yang Y., RA Young-Bellido M., Zhao G., Zook C., Baltz R.H., Jaskunas S.Richard., RA Rosteck P.R.Jr., Skatrud P.L., Glass J.I.; RT "Genome of the bacterium Streptococcus pneumoniae strain R6."; RL J. Bacteriol. 183:5709-5717(2001). RN [2] {ECO:0007829|PDB:3Q1L} RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS). RX PubMed=22039970; DOI=10.1111/j.1747-0285.2011.01267.x; RA Pavlovsky A.G., Liu X., Faehnle C.R., Potente N., Viola R.E.; RT "Structural characterization of inhibitors with selectivity against members RT of a homologous enzyme family."; RL Chem. Biol. Drug Des. 79:128-136(2012). RN [3] {ECO:0007829|PDB:4R3N} RP X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) IN COMPLEX WITH NADP(+). RX PubMed=25478842; DOI=10.1107/S1399004714023979; RA Pavlovsky A.G., Thangavelu B., Bhansali P., Viola R.E.; RT "A cautionary tale of structure-guided inhibitor development against an RT essential enzyme in the aspartate-biosynthetic pathway."; RL Acta Crystallogr. D 70:3244-3252(2014). CC -!- FUNCTION: Catalyzes the NADPH-dependent formation of L-aspartate- CC semialdehyde (L-ASA) by the reductive dephosphorylation of L-aspartyl- CC 4-phosphate. {ECO:0000256|HAMAP-Rule:MF_02121}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-aspartate 4-semialdehyde + NADP(+) + phosphate = 4-phospho- CC L-aspartate + H(+) + NADPH; Xref=Rhea:RHEA:24284, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57535, ChEBI:CHEBI:57783, CC ChEBI:CHEBI:58349, ChEBI:CHEBI:537519; EC=1.2.1.11; CC Evidence={ECO:0000256|ARBA:ARBA00001636, ECO:0000256|HAMAP- CC Rule:MF_02121}; CC -!- PATHWAY: Amino-acid biosynthesis; L-lysine biosynthesis via DAP CC pathway; (S)-tetrahydrodipicolinate from L-aspartate: step 2/4. CC {ECO:0000256|ARBA:ARBA00005076, ECO:0000256|HAMAP-Rule:MF_02121}. CC -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via de novo CC pathway; L-homoserine from L-aspartate: step 2/3. CC {ECO:0000256|ARBA:ARBA00005021, ECO:0000256|HAMAP-Rule:MF_02121}. CC -!- PATHWAY: Amino-acid biosynthesis; L-threonine biosynthesis; L-threonine CC from L-aspartate: step 2/5. {ECO:0000256|ARBA:ARBA00005097, CC ECO:0000256|HAMAP-Rule:MF_02121}. CC -!- SUBUNIT: Homodimer. {ECO:0000256|ARBA:ARBA00011738, ECO:0000256|HAMAP- CC Rule:MF_02121}. CC -!- SIMILARITY: Belongs to the aspartate-semialdehyde dehydrogenase family. CC {ECO:0000256|ARBA:ARBA00010584, ECO:0000256|HAMAP-Rule:MF_02121}. CC -!- CAUTION: Lacks conserved residue(s) required for the propagation of CC feature annotation. {ECO:0000256|HAMAP-Rule:MF_02121}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AE007317; AAK99722.1; -; Genomic_DNA. DR PIR; F97986; F97986. DR RefSeq; NP_358512.1; NC_003098.1. DR RefSeq; WP_000542475.1; NC_003098.1. DR PDB; 3Q1L; X-ray; 2.30 A; A/B/C/D=1-358. DR PDB; 4R3N; X-ray; 1.35 A; A/B=1-358. DR PDBsum; 3Q1L; -. DR PDBsum; 4R3N; -. DR AlphaFoldDB; Q8DQ00; -. DR SMR; Q8DQ00; -. DR STRING; 171101.spr0918; -. DR EnsemblBacteria; AAK99722; AAK99722; spr0918. DR GeneID; 66806138; -. DR KEGG; spr:spr0918; -. DR PATRIC; fig|171101.6.peg.1005; -. DR eggNOG; COG0136; Bacteria. DR HOGENOM; CLU_049966_0_1_9; -. DR OMA; CEEEMKM; -. DR UniPathway; UPA00034; UER00016. DR UniPathway; UPA00050; UER00463. DR UniPathway; UPA00051; UER00464. DR Proteomes; UP000000586; Chromosome. DR GO; GO:0004073; F:aspartate-semialdehyde dehydrogenase activity; IEA:UniProtKB-UniRule. DR GO; GO:0051287; F:NAD binding; IEA:InterPro. DR GO; GO:0050661; F:NADP binding; IEA:UniProtKB-UniRule. DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro. DR GO; GO:0071266; P:'de novo' L-methionine biosynthetic process; IEA:UniProtKB-UniRule. DR GO; GO:0019877; P:diaminopimelate biosynthetic process; IEA:UniProtKB-UniRule. DR GO; GO:0009097; P:isoleucine biosynthetic process; IEA:InterPro. DR GO; GO:0009089; P:lysine biosynthetic process via diaminopimelate; IEA:UniProtKB-UniRule. DR GO; GO:0009088; P:threonine biosynthetic process; IEA:UniProtKB-UniRule. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. DR HAMAP; MF_02121; ASADH; 1. DR InterPro; IPR012080; Asp_semialdehyde_DH. DR InterPro; IPR005986; Asp_semialdehyde_DH_beta. DR InterPro; IPR036291; NAD(P)-bd_dom_sf. DR InterPro; IPR000534; Semialdehyde_DH_NAD-bd. DR InterPro; IPR012280; Semialdhyde_DH_dimer_dom. DR NCBIfam; TIGR01296; asd_B; 1. DR PANTHER; PTHR46278:SF2; ASPARTATE-SEMIALDEHYDE DEHYDROGENASE; 1. DR PANTHER; PTHR46278; DEHYDROGENASE, PUTATIVE-RELATED; 1. DR Pfam; PF01118; Semialdhyde_dh; 1. DR Pfam; PF02774; Semialdhyde_dhC; 1. DR PIRSF; PIRSF000148; ASA_dh; 1. DR SMART; SM00859; Semialdhyde_dh; 1. DR SUPFAM; SSF55347; Glyceraldehyde-3-phosphate dehydrogenase-like, C-terminal domain; 1. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. PE 1: Evidence at protein level; KW 3D-structure {ECO:0007829|PDB:3Q1L, ECO:0007829|PDB:4R3N}; KW Amino-acid biosynthesis {ECO:0000256|HAMAP-Rule:MF_02121}; KW Diaminopimelate biosynthesis {ECO:0000256|ARBA:ARBA00022915, KW ECO:0000256|HAMAP-Rule:MF_02121}; KW Lysine biosynthesis {ECO:0000256|ARBA:ARBA00023154, ECO:0000256|HAMAP- KW Rule:MF_02121}; KW Methionine biosynthesis {ECO:0000256|ARBA:ARBA00023167, ECO:0000256|HAMAP- KW Rule:MF_02121}; NADP {ECO:0000256|HAMAP-Rule:MF_02121}; KW Nucleotide-binding {ECO:0007829|PDB:4R3N}; KW Oxidoreductase {ECO:0000256|HAMAP-Rule:MF_02121, KW ECO:0000313|EMBL:AAK99722.1}; KW Reference proteome {ECO:0000313|Proteomes:UP000000586}; KW Threonine biosynthesis {ECO:0000256|ARBA:ARBA00022697, ECO:0000256|HAMAP- KW Rule:MF_02121}. FT DOMAIN 4..119 FT /note="Semialdehyde dehydrogenase NAD-binding" FT /evidence="ECO:0000259|SMART:SM00859" FT ACT_SITE 128 FT /note="Acyl-thioester intermediate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_02121, FT ECO:0000256|PIRSR:PIRSR000148-1" FT ACT_SITE 252 FT /note="Proton acceptor" FT /evidence="ECO:0000256|HAMAP-Rule:MF_02121, FT ECO:0000256|PIRSR:PIRSR000148-1" FT BINDING 9 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0007829|PDB:4R3N" FT BINDING 11..14 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000256|HAMAP-Rule:MF_02121" FT BINDING 11 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0007829|PDB:4R3N" FT BINDING 12 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0007829|PDB:4R3N" FT BINDING 13 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0007829|PDB:4R3N" FT BINDING 14 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0007829|PDB:4R3N" FT BINDING 36 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0007829|PDB:4R3N" FT BINDING 37 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0007829|PDB:4R3N" FT BINDING 39..40 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000256|HAMAP-Rule:MF_02121" FT BINDING 39 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0007829|PDB:4R3N" FT BINDING 40 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0007829|PDB:4R3N" FT BINDING 71 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0007829|PDB:4R3N" FT BINDING 94 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0007829|PDB:4R3N" FT BINDING 99 FT /ligand="phosphate" FT /ligand_id="ChEBI:CHEBI:43474" FT /evidence="ECO:0000256|HAMAP-Rule:MF_02121" FT BINDING 126 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0007829|PDB:4R3N" FT BINDING 128 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0007829|PDB:4R3N" FT BINDING 155 FT /ligand="substrate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_02121" FT BINDING 158..159 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000256|HAMAP-Rule:MF_02121" FT BINDING 162 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0007829|PDB:4R3N" FT BINDING 163 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0007829|PDB:4R3N" FT BINDING 245 FT /ligand="substrate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_02121" FT BINDING 325 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000256|HAMAP-Rule:MF_02121" FT BINDING 329 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0007829|PDB:4R3N" SQ SEQUENCE 358 AA; 38924 MW; 366715956847C96C CRC64; MGYTVAVVGA TGAVGAQMIK MLEESTLPID KIRYLASARS AGKSLKFKDQ DITIEETTET AFEGVDIALF SAGSSTSAKY APYAVKAGVV VVDNTSYFRQ NPDVPLVVPE VNAHALDAHN GIIACPNCST IQMMVALEPV RQKWGLDRII VSTYQAVSGA GMGAILETQR ELREVLNDGV KPCDLHAEIL PSGGDKKHYP IAFNALPQID VFTDNDYTYE EMKMTKETKK IMEDDSIAVS ATCVRIPVLS AHSESVYIET KEVAPIEEVK AAIAAFPGAV LEDDVAHQIY PQAINAVGSR DTFVGRIRKD LDAEKGIHMW VVSDNLLKGA AWNSVQIAET LHERGLVRPT AELKFELK //