DHOM_MYCTU
ID DHOM_MYCTU Reviewed; 441 AA.
AC P9WPX1; L0T681; P63629; Q10601;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 44.
DE RecName: Full=Homoserine dehydrogenase;
DE Short=HDH;
DE EC=1.1.1.3;
GN Name=hom; Synonyms=thrA; OrderedLocusNames=Rv1294; ORFNames=MTCY373.14;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-homoserine + NADP(+) = H(+) + L-aspartate 4-semialdehyde +
CC NADPH; Xref=Rhea:RHEA:15761, ChEBI:CHEBI:15378, ChEBI:CHEBI:57476,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:537519; EC=1.1.1.3;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-homoserine + NAD(+) = H(+) + L-aspartate 4-semialdehyde +
CC NADH; Xref=Rhea:RHEA:15757, ChEBI:CHEBI:15378, ChEBI:CHEBI:57476,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:537519; EC=1.1.1.3;
CC -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via de novo
CC pathway; L-homoserine from L-aspartate: step 3/3.
CC -!- PATHWAY: Amino-acid biosynthesis; L-threonine biosynthesis; L-threonine
CC from L-aspartate: step 3/5.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the homoserine dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP44051.1; -; Genomic_DNA.
DR PIR; B70773; B70773.
DR RefSeq; NP_215810.1; NC_000962.3.
DR RefSeq; WP_003406648.1; NZ_NVQJ01000030.1.
DR AlphaFoldDB; P9WPX1; -.
DR SMR; P9WPX1; -.
DR STRING; 83332.Rv1294; -.
DR PaxDb; P9WPX1; -.
DR DNASU; 886962; -.
DR GeneID; 45425268; -.
DR GeneID; 886962; -.
DR KEGG; mtu:Rv1294; -.
DR TubercuList; Rv1294; -.
DR eggNOG; COG0460; Bacteria.
DR OMA; LMFYGPG; -.
DR PhylomeDB; P9WPX1; -.
DR UniPathway; UPA00050; UER00063.
DR UniPathway; UPA00051; UER00465.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0004412; F:homoserine dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR GO; GO:0009097; P:isoleucine biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0009086; P:methionine biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0009088; P:threonine biosynthetic process; IBA:GO_Central.
DR InterPro; IPR045865; ACT-like_dom_sf.
DR InterPro; IPR002912; ACT_dom.
DR InterPro; IPR005106; Asp/hSer_DH_NAD-bd.
DR InterPro; IPR016204; HDH.
DR InterPro; IPR001342; HDH_cat.
DR InterPro; IPR019811; HDH_CS.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF01842; ACT; 1.
DR Pfam; PF00742; Homoserine_dh; 1.
DR Pfam; PF03447; NAD_binding_3; 1.
DR PIRSF; PIRSF000098; Homoser_dehydrog; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF55021; SSF55021; 1.
DR PROSITE; PS51671; ACT; 1.
DR PROSITE; PS01042; HOMOSER_DHGENASE; 1.
PE 1: Evidence at protein level;
KW Amino-acid biosynthesis; Branched-chain amino acid biosynthesis;
KW Isoleucine biosynthesis; Methionine biosynthesis; NADP; Oxidoreductase;
KW Reference proteome; Threonine biosynthesis.
FT CHAIN 1..441
FT /note="Homoserine dehydrogenase"
FT /id="PRO_0000066702"
FT DOMAIN 356..435
FT /note="ACT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01007"
FT ACT_SITE 207
FT /note="Proton donor"
FT /evidence="ECO:0000255"
FT BINDING 13..20
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 107
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 192
FT /ligand="substrate"
FT /evidence="ECO:0000250"
SQ SEQUENCE 441 AA; 45553 MW; 818248C137885BE8 CRC64;
MPGDEKPVGV AVLGLGNVGS EVVRIIENSA EDLAARVGAP LVLRGIGVRR VTTDRGVPIE
LLTDDIEELV AREDVDIVVE VMGPVEPSRK AILGALERGK SVVTANKALL ATSTGELAQA
AESAHVDLYF EAAVAGAIPV IRPLTQSLAG DTVLRVAGIV NGTTNYILSA MDSTGADYAS
ALADASALGY AEADPTADVE GYDAAAKAAI LASIAFHTRV TADDVYREGI TKVTPADFGS
AHALGCTIKL LSICERITTD EGSQRVSARV YPALVPLSHP LAAVNGAFNA VVVEAEAAGR
LMFYGQGAGG APTASAVTGD LVMAARNRVL GSRGPRESKY AQLPVAPMGF IETRYYVSMN
VADKPGVLSA VAAEFAKREV SIAEVRQEGV VDEGGRRVGA RIVVVTHLAT DAALSETVDA
LDDLDVVQGV SSVIRLEGTG L
