MABA_MYCTU
ID MABA_MYCTU Reviewed; 247 AA.
AC P9WGT3; L0T9R6; P0A5Y4; P71764; Q48930;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 45.
DE RecName: Full=3-oxoacyl-[acyl-carrier-protein] reductase MabA {ECO:0000305};
DE EC=1.1.1.100 {ECO:0000305|PubMed:19685079};
DE AltName: Full=3-ketoacyl reductase {ECO:0000303|PubMed:9802011};
DE AltName: Full=3-ketoacyl-acyl carrier protein reductase;
DE AltName: Full=Acetoacetyl-CoA reductase;
DE EC=1.1.1.36 {ECO:0000269|PubMed:11932442, ECO:0000269|PubMed:17059223, ECO:0000269|PubMed:18155153, ECO:0000269|PubMed:9802011};
DE AltName: Full=Beta-ketoacyl-acyl carrier protein reductase;
DE Short=Beta-ketoacyl-ACP reductase {ECO:0000303|PubMed:11932442};
DE AltName: Full=Mycolic acid biosynthesis A {ECO:0000303|PubMed:9802011};
GN Name=mabA {ECO:0000303|PubMed:9802011};
GN Synonyms=fabG1 {ECO:0000303|PubMed:11932442}; OrderedLocusNames=Rv1483;
GN ORFNames=MTCY277.04;
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 [GENOMIC DNA], FUNCTION AS A BETA-KETOACYL-COA
RP REDUCTASE, AND CATALYTIC ACTIVITY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9802011; DOI=10.1099/00221287-144-10-2697;
RA Banerjee A., Sugantino M., Sacchettini J.C., Jacobs W.R. Jr.;
RT "The mabA gene from the inhA operon of Mycobacterium tuberculosis encodes a
RT 3-ketoacyl reductase that fails to confer isoniazid resistance.";
RL Microbiology 144:2697-2704(1998).
RN [2]
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 [3]
RP FUNCTION IN MYCOLIC ACID BIOSYNTHESIS, CATALYTIC ACTIVITY, MASS
RP SPECTROMETRY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP PATHWAY, SUBUNIT, AND SUBCELLULAR LOCATION.
RC STRAIN=H37Rv;
RX PubMed=11932442; DOI=10.1099/00221287-148-4-951;
RA Marrakchi H., Ducasse S., Labesse G., Montrozier H., Margeat E.,
RA Emorine L., Charpentier X., Daffe M., Quemard A.;
RT "MabA (FabG1), a Mycobacterium tuberculosis protein involved in the long-
RT chain fatty acid elongation system FAS-II.";
RL Microbiology 148:951-960(2002).
RN [4]
RP ACTIVITY REGULATION, AND MUTAGENESIS OF TYR-185.
RX PubMed=14693546; DOI=10.1128/aac.48.1.242-249.2004;
RA Ducasse-Cabanot S., Cohen-Gonsaud M., Marrakchi H., Nguyen M., Zerbib D.,
RA Bernadou J., Daffe M., Labesse G., Quemard A.;
RT "In vitro inhibition of the Mycobacterium tuberculosis beta-ketoacyl-acyl
RT carrier protein reductase MabA by isoniazid.";
RL Antimicrob. Agents Chemother. 48:242-249(2004).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, REACTION MECHANISM, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND SUBUNIT.
RX PubMed=17059223; DOI=10.1021/bi0611210;
RA Silva R.G., de Carvalho L.P., Blanchard J.S., Santos D.S., Basso L.A.;
RT "Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein (ACP)
RT reductase: kinetic and chemical mechanisms.";
RL Biochemistry 45:13064-13073(2006).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, REACTION MECHANISM, AND SUBUNIT.
RX PubMed=18155153; DOI=10.1016/j.abb.2007.12.002;
RA Silva R.G., Rosado L.A., Santos D.S., Basso L.A.;
RT "Mycobacterium tuberculosis beta-ketoacyl-ACP reductase: alpha-secondary
RT kinetic isotope effects and kinetic and equilibrium mechanisms of substrate
RT binding.";
RL Arch. Biochem. Biophys. 471:1-10(2008).
RN [7]
RP FUNCTION AS A BETA-KETOACYL-ACP REDUCTASE, AND CATALYTIC ACTIVITY.
RX PubMed=19685079; DOI=10.1007/s00438-009-0474-2;
RA Gurvitz A.;
RT "The essential mycobacterial genes, fabG1 and fabG4, encode 3-oxoacyl-
RT thioester reductases that are functional in yeast mitochondrial fatty acid
RT synthase type 2.";
RL Mol. Genet. Genomics 282:407-416(2009).
RN [8]
RP PHOSPHORYLATION AT THR-21; THR-114 AND THR-191, ACTIVITY REGULATION,
RP PATHWAY, AND MUTAGENESIS OF THR-21; THR-114 AND THR-191.
RX PubMed=20178986; DOI=10.1074/jbc.m110.105189;
RA Veyron-Churlet R., Zanella-Cleon I., Cohen-Gonsaud M., Molle V., Kremer L.;
RT "Phosphorylation of the Mycobacterium tuberculosis beta-ketoacyl-acyl
RT carrier protein reductase MabA regulates mycolic acid biosynthesis.";
RL J. Biol. Chem. 285:12714-12725(2010).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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).
RN [10]
RP MUTAGENESIS OF SER-140.
RX PubMed=23006410; DOI=10.1186/1756-0500-5-526;
RA Rosado L.A., Caceres R.A., de Azevedo W.F. Jr., Basso L.A., Santos D.S.;
RT "Role of Serine140 in the mode of action of Mycobacterium tuberculosis
RT beta-ketoacyl-ACP Reductase (MabA).";
RL BMC Res. Notes 5:526-526(2012).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF WILD-TYPE AND MUTANT VAL-60,
RP MUTAGENESIS OF CYS-60, SUBUNIT, AND NOMENCLATURE.
RX PubMed=12079383; DOI=10.1016/s0022-2836(02)00463-1;
RA Cohen-Gonsaud M., Ducasse S., Hoh F., Zerbib D., Labesse G., Quemard A.;
RT "Crystal structure of MabA from Mycobacterium tuberculosis, a reductase
RT involved in long-chain fatty acid biosynthesis.";
RL J. Mol. Biol. 320:249-261(2002).
RN [12] {ECO:0007744|PDB:1UZL, ECO:0007744|PDB:1UZM, ECO:0007744|PDB:1UZN}
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF APOENZYME; MUTANT VAL-60 AND
RP MUTANT VAL-60/LEU-144 IN COMPLEX WITH NADP, SUBUNIT, DOMAIN, AND
RP MUTAGENESIS OF CYS-60; GLY-139 AND SER-144.
RX PubMed=15977159; DOI=10.1002/prot.20494;
RA Cohen-Gonsaud M., Ducasse-Cabanot S., Quemard A., Labesse G.;
RT "Ligand-induced fit in mycobacterial MabA: the sequence-specific C-terminus
RT locks the conformational change.";
RL Proteins 60:392-400(2005).
RN [13] {ECO:0007744|PDB:2NTN}
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF MUTANT VAL-60/ALA-139/LEU-144,
RP MUTAGENESIS OF CYS-60; GLY-139 AND SER-144, AND SUBUNIT.
RX PubMed=17642518; DOI=10.1107/s0907444907024158;
RA Poncet-Montange G., Ducasse-Cabanot S., Quemard A., Labesse G.,
RA Cohen-Gonsaud M.;
RT "Lack of dynamics in the MabA active site kills the enzyme activity:
RT practical consequences for drug-design studies.";
RL Acta Crystallogr. D 63:923-925(2007).
CC -!- FUNCTION: Part of the mycobacterial fatty acid elongation system FAS-
CC II, which is involved in mycolic acid biosynthesis (PubMed:11932442).
CC Catalyzes the NADPH-dependent reduction of beta-ketoacyl derivatives,
CC the second step of the FAS-II elongation cycle (PubMed:9802011,
CC PubMed:11932442, PubMed:17059223, PubMed:18155153, PubMed:19685079).
CC May preferentially metabolize long-chain substrates (C8-C20)
CC (PubMed:11932442). Can use CoA derivatives as substrates in vitro
CC (PubMed:9802011, PubMed:11932442, PubMed:17059223, PubMed:18155153).
CC {ECO:0000269|PubMed:11932442, ECO:0000269|PubMed:17059223,
CC ECO:0000269|PubMed:18155153, ECO:0000269|PubMed:19685079,
CC ECO:0000269|PubMed:9802011}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3R)-hydroxyacyl-[ACP] + NADP(+) = a 3-oxoacyl-[ACP] + H(+)
CC + NADPH; Xref=Rhea:RHEA:17397, Rhea:RHEA-COMP:9916, Rhea:RHEA-
CC COMP:9945, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:78776, ChEBI:CHEBI:78827; EC=1.1.1.100;
CC Evidence={ECO:0000305|PubMed:19685079};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:17399;
CC Evidence={ECO:0000305|PubMed:19685079};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3R)-3-hydroxyacyl-CoA + NADP(+) = a 3-oxoacyl-CoA + H(+) +
CC NADPH; Xref=Rhea:RHEA:22256, ChEBI:CHEBI:15378, ChEBI:CHEBI:57319,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:90726; EC=1.1.1.36;
CC Evidence={ECO:0000269|PubMed:11932442, ECO:0000269|PubMed:17059223,
CC ECO:0000269|PubMed:18155153, ECO:0000269|PubMed:9802011};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:22258;
CC Evidence={ECO:0000269|PubMed:11932442, ECO:0000269|PubMed:17059223,
CC ECO:0000269|PubMed:18155153, ECO:0000269|PubMed:9802011};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R)-3-hydroxybutanoyl-CoA + NADP(+) = acetoacetyl-CoA + H(+)
CC + NADPH; Xref=Rhea:RHEA:45796, ChEBI:CHEBI:15378, ChEBI:CHEBI:57286,
CC ChEBI:CHEBI:57315, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000269|PubMed:11932442, ECO:0000269|PubMed:17059223,
CC ECO:0000269|PubMed:18155153, ECO:0000269|PubMed:9802011};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:45798;
CC Evidence={ECO:0000269|PubMed:11932442, ECO:0000269|PubMed:17059223,
CC ECO:0000269|PubMed:18155153, ECO:0000269|PubMed:9802011};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R)-hydroxyoctanoyl-CoA + NADP(+) = 3-oxooctanoyl-CoA + H(+)
CC + NADPH; Xref=Rhea:RHEA:45844, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:62619, ChEBI:CHEBI:74279;
CC Evidence={ECO:0000269|PubMed:11932442};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:45846;
CC Evidence={ECO:0000269|PubMed:11932442};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R)-3-hydroxydodecanoyl-CoA + NADP(+) = 3-oxododecanoyl-CoA +
CC H(+) + NADPH; Xref=Rhea:RHEA:45848, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:62615,
CC ChEBI:CHEBI:74276; Evidence={ECO:0000269|PubMed:11932442};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:45850;
CC Evidence={ECO:0000269|PubMed:11932442};
CC -!- ACTIVITY REGULATION: Phosphorylation alters the activity, and
CC subsequently mycolic acid biosynthesis (PubMed:20178986). In vitro,
CC activity is efficiently inhibited by isoniazid. Acts by forming an
CC isonicotinoyl-NADP adduct that binds to the MabA active site
CC (PubMed:14693546). {ECO:0000269|PubMed:14693546,
CC ECO:0000269|PubMed:20178986}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=8.3 uM for beta-ketododecanoyl-CoA (at 25 degrees Celsius and at
CC pH 7.0) {ECO:0000269|PubMed:11932442};
CC KM=70 uM for beta-ketooctanoyl-CoA (at 25 degrees Celsius and at pH
CC 7.0) {ECO:0000269|PubMed:11932442};
CC KM=1530 uM for acetoacetyl-CoA (at 25 degrees Celsius and at pH 7.0)
CC {ECO:0000269|PubMed:11932442};
CC KM=165 uM for acetoacetyl-CoA {ECO:0000269|PubMed:17059223};
CC KM=41 uM for NADPH (at 25 degrees Celsius and at pH 7.0)
CC {ECO:0000269|PubMed:11932442};
CC KM=26 uM for NADPH {ECO:0000269|PubMed:17059223};
CC Note=kcat is 4.3 sec(-1) with beta-ketododecanoyl-CoA as substrate.
CC kcat is 3.5 sec(-1) with beta-ketooctanoyl-CoA as substrate. kcat is
CC 1.9 sec(-1) with acetoacetyl-CoA as substrate. kcat is 2.6 sec(-1)
CC with NADPH as substrate (PubMed:11932442). kcat is 7 sec(-1) with
CC acetoacetyl-CoA as substrate (PubMed:17059223).
CC {ECO:0000269|PubMed:11932442, ECO:0000269|PubMed:17059223};
CC -!- PATHWAY: Lipid metabolism; mycolic acid biosynthesis.
CC {ECO:0000269|PubMed:20178986, ECO:0000305|PubMed:11932442}.
CC -!- SUBUNIT: Homotetramer (PubMed:11932442, PubMed:12079383,
CC PubMed:15977159, PubMed:17642518). Homodimer in solution
CC (PubMed:17059223, PubMed:18155153). {ECO:0000269|PubMed:11932442,
CC ECO:0000269|PubMed:12079383, ECO:0000269|PubMed:15977159,
CC ECO:0000269|PubMed:17059223, ECO:0000269|PubMed:17642518,
CC ECO:0000269|PubMed:18155153}.
CC -!- SUBCELLULAR LOCATION: Secreted, cell wall
CC {ECO:0000269|PubMed:11932442}.
CC -!- DOMAIN: Shows a significant rearrangement of the active site between a
CC closed inactive conformation and an open and active form in presence of
CC NADP. The C-terminus adopts a particular conformation that locks the
CC conformational changes. {ECO:0000269|PubMed:15977159}.
CC -!- PTM: Efficiently phosphorylated in vitro by several M.tuberculosis
CC Ser/Thr protein kinases (STPKs), including PknA, PknB, PknD, PknE, and
CC PknL. Thr-191 represents the primary phosphorylation site in vivo.
CC {ECO:0000269|PubMed:20178986}.
CC -!- MASS SPECTROMETRY: Mass=27729; Method=Electrospray; Note=Recombinant
CC protein expressed in E.coli.; Evidence={ECO:0000269|PubMed:11932442};
CC -!- MISCELLANEOUS: Restores respiratory growth of S.cerevisiae oar1
CC deletion mutant. {ECO:0000269|PubMed:19685079}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; U66801; AAC69639.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP44243.1; -; Genomic_DNA.
DR PIR; F70710; F70710.
DR RefSeq; NP_215999.1; NC_000962.3.
DR RefSeq; WP_003898892.1; NZ_NVQJ01000004.1.
DR PDB; 1UZL; X-ray; 2.00 A; A/B=1-247.
DR PDB; 1UZM; X-ray; 1.49 A; A/B=1-247.
DR PDB; 1UZN; X-ray; 1.91 A; A/B=1-247.
DR PDB; 2NTN; X-ray; 2.30 A; A/B=1-247.
DR PDBsum; 1UZL; -.
DR PDBsum; 1UZM; -.
DR PDBsum; 1UZN; -.
DR PDBsum; 2NTN; -.
DR AlphaFoldDB; P9WGT3; -.
DR SMR; P9WGT3; -.
DR STRING; 83332.Rv1483; -.
DR SwissLipids; SLP:000001159; -.
DR iPTMnet; P9WGT3; -.
DR PaxDb; P9WGT3; -.
DR DNASU; 886551; -.
DR GeneID; 45425462; -.
DR GeneID; 886551; -.
DR KEGG; mtu:Rv1483; -.
DR TubercuList; Rv1483; -.
DR eggNOG; COG1028; Bacteria.
DR OMA; KMPERDY; -.
DR PhylomeDB; P9WGT3; -.
DR BRENDA; 1.1.1.100; 3445.
DR UniPathway; UPA00915; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0004316; F:3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity; IDA:MTBBASE.
DR GO; GO:0018454; F:acetoacetyl-CoA reductase activity; IDA:MTBBASE.
DR GO; GO:0070402; F:NADPH binding; IDA:UniProtKB.
DR GO; GO:0071768; P:mycolic acid biosynthetic process; IDA:MTBBASE.
DR GO; GO:0046459; P:short-chain fatty acid metabolic process; IDA:MTBBASE.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cell wall; Fatty acid biosynthesis;
KW Fatty acid metabolism; Lipid biosynthesis; Lipid metabolism; NADP;
KW Oxidoreductase; Phosphoprotein; Reference proteome; Secreted.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:11932442,
FT ECO:0007744|PubMed:21969609"
FT CHAIN 2..247
FT /note="3-oxoacyl-[acyl-carrier-protein] reductase MabA"
FT /id="PRO_0000054677"
FT ACT_SITE 153
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 25..27
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:15977159,
FT ECO:0007744|PDB:1UZN"
FT BINDING 47
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:15977159,
FT ECO:0007744|PDB:1UZN"
FT BINDING 61..62
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:15977159,
FT ECO:0007744|PDB:1UZN"
FT BINDING 90
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:15977159,
FT ECO:0007744|PDB:1UZN"
FT BINDING 153
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P71534"
FT BINDING 157
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P71534"
FT BINDING 186
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P71534"
FT BINDING 197
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P71534"
FT SITE 140
FT /note="Important for activity"
FT /evidence="ECO:0000305|PubMed:23006410"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0007744|PubMed:21969609"
FT MOD_RES 21
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:20178986"
FT MOD_RES 114
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:20178986"
FT MOD_RES 191
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:20178986"
FT MUTAGEN 21
FT /note="T->A: Slight decrease in phosphorylation by PknB.
FT Lack of phosphorylation by PknB; when associated with A-114
FT and A-191."
FT /evidence="ECO:0000269|PubMed:20178986"
FT MUTAGEN 60
FT /note="C->V: Displays a lower activity than the wild-type
FT and a slightly decreased affinity for the cofactor. Retains
FT 84% of activity; when associated with L-144. Totally
FT inactive; when associated with A-139 and L-144."
FT /evidence="ECO:0000269|PubMed:12079383,
FT ECO:0000269|PubMed:15977159, ECO:0000269|PubMed:17642518"
FT MUTAGEN 114
FT /note="T->A: Slight decrease in phosphorylation by PknB.
FT Lack of phosphorylation by PknB; when associated with A-21
FT and A-191."
FT /evidence="ECO:0000269|PubMed:20178986"
FT MUTAGEN 139
FT /note="G->A: Complete protein inactivation and freezes the
FT catalytic site into its closed form. Totally inactive; when
FT associated with V-60 and L-144."
FT /evidence="ECO:0000269|PubMed:15977159,
FT ECO:0000269|PubMed:17642518"
FT MUTAGEN 140
FT /note="S->A: Loss of activity. Can still bind NADPH."
FT /evidence="ECO:0000269|PubMed:23006410"
FT MUTAGEN 140
FT /note="S->T: Loss of activity. Impaired NADPH binding."
FT /evidence="ECO:0000269|PubMed:23006410"
FT MUTAGEN 144
FT /note="S->L: Stabilizes the catalytic loop in its open
FT active form. Retains 84% of activity; when associated with
FT V-60. Totally inactive; when associated with V-60 and A-
FT 139."
FT /evidence="ECO:0000269|PubMed:15977159,
FT ECO:0000269|PubMed:17642518"
FT MUTAGEN 185
FT /note="Y->L: 70% decrease in activity with acetoacetyl-CoA
FT as substrate. Does not affect NADP binding."
FT /evidence="ECO:0000269|PubMed:14693546"
FT MUTAGEN 191
FT /note="T->A: Retains 22% of wild-type reductase activity.
FT Strong decrease in phosphorylation by PknB. Lack of
FT phosphorylation by PknB; when associated with A-21 and A-
FT 114."
FT /evidence="ECO:0000269|PubMed:20178986"
FT MUTAGEN 191
FT /note="T->D: Phosphomimetic mutant that retains less than
FT 10% of wild-type reductase activity. Impaired NADPH
FT binding. Overproduction of the mutant leads to a
FT significant inhibition of de novo biosynthesis of mycolic
FT acids."
FT /evidence="ECO:0000269|PubMed:20178986"
FT STRAND 17..20
FT /evidence="ECO:0007829|PDB:1UZM"
FT TURN 21..24
FT /evidence="ECO:0007829|PDB:1UZM"
FT HELIX 26..37
FT /evidence="ECO:0007829|PDB:1UZM"
FT STRAND 41..49
FT /evidence="ECO:0007829|PDB:1UZM"
FT STRAND 55..59
FT /evidence="ECO:0007829|PDB:1UZM"
FT HELIX 65..79
FT /evidence="ECO:0007829|PDB:1UZM"
FT STRAND 83..88
FT /evidence="ECO:0007829|PDB:1UZM"
FT TURN 97..99
FT /evidence="ECO:0007829|PDB:1UZN"
FT HELIX 102..112
FT /evidence="ECO:0007829|PDB:1UZM"
FT HELIX 114..129
FT /evidence="ECO:0007829|PDB:1UZM"
FT STRAND 133..138
FT /evidence="ECO:0007829|PDB:1UZM"
FT HELIX 142..145
FT /evidence="ECO:0007829|PDB:1UZN"
FT HELIX 151..171
FT /evidence="ECO:0007829|PDB:1UZM"
FT HELIX 172..174
FT /evidence="ECO:0007829|PDB:1UZM"
FT STRAND 176..183
FT /evidence="ECO:0007829|PDB:1UZM"
FT HELIX 189..193
FT /evidence="ECO:0007829|PDB:1UZM"
FT HELIX 196..202
FT /evidence="ECO:0007829|PDB:1UZM"
FT HELIX 203..205
FT /evidence="ECO:0007829|PDB:1UZM"
FT HELIX 214..225
FT /evidence="ECO:0007829|PDB:1UZM"
FT HELIX 227..229
FT /evidence="ECO:0007829|PDB:1UZM"
FT STRAND 236..240
FT /evidence="ECO:0007829|PDB:1UZM"
FT TURN 241..244
FT /evidence="ECO:0007829|PDB:1UZM"
SQ SEQUENCE 247 AA; 25697 MW; 70F6254B0FFFCD47 CRC64;
MTATATEGAK PPFVSRSVLV TGGNRGIGLA IAQRLAADGH KVAVTHRGSG APKGLFGVEC
DVTDSDAVDR AFTAVEEHQG PVEVLVSNAG LSADAFLMRM TEEKFEKVIN ANLTGAFRVA
QRASRSMQRN KFGRMIFIGS VSGSWGIGNQ ANYAASKAGV IGMARSIARE LSKANVTANV
VAPGYIDTDM TRALDERIQQ GALQFIPAKR VGTPAEVAGV VSFLASEDAS YISGAVIPVD
GGMGMGH
