FPRA_MYCTU
ID FPRA_MYCTU Reviewed; 456 AA.
AC P9WIQ3; L0TBK5; O05783;
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=NADPH-ferredoxin reductase FprA;
DE Short=NFR;
DE EC=1.18.1.2 {ECO:0000269|PubMed:12071965};
GN Name=fprA {ECO:0000303|PubMed:12071965}; OrderedLocusNames=Rv3106;
GN ORFNames=MTCY164.16;
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 PROTEIN SEQUENCE OF 1-21, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, COFACTOR, AND SUBUNIT.
RX PubMed=12071965; DOI=10.1046/j.1432-1033.2002.02989.x;
RA Fischer F., Raimondi D., Aliverti A., Zanetti G.;
RT "Mycobacterium tuberculosis FprA, a novel bacterial NADPH-ferredoxin
RT reductase.";
RL Eur. J. Biochem. 269:3005-3013(2002).
RN [3]
RP ENZYME KINETICS, REDOX POTENTIOMETRY, ABSORPTION SPECTROSCOPY, CIRCULAR
RP DICHROISM ANALYSIS, AND EPR SPECTROSCOPY.
RX PubMed=12614197; DOI=10.1042/bj20021692;
RA McLean K.J., Scrutton N.S., Munro A.W.;
RT "Kinetic, spectroscopic and thermodynamic characterization of the
RT Mycobacterium tuberculosis adrenodoxin reductase homologue FprA.";
RL Biochem. J. 372:317-327(2003).
RN [4]
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).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.05 ANGSTROMS) IN COMPLEX WITH NADP, AND SUBUNIT.
RX PubMed=12102623; DOI=10.1021/bi025858a;
RA Bossi R.T., Aliverti A., Raimondi D., Fischer F., Zanetti G., Ferrari D.,
RA Tahallah N., Maier C.S., Heck A.J., Rizzi M., Mattevi A.;
RT "A covalent modification of NADP+ revealed by the atomic resolution
RT structure of FprA, a Mycobacterium tuberculosis oxidoreductase.";
RL Biochemistry 41:8807-8818(2002).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF MUTANT GLN-57 IN COMPLEX WITH FAD
RP AND NADPH, AND SUBUNIT.
RX PubMed=16846214; DOI=10.1021/bi060369m;
RA Pennati A., Razeto A., de Rosa M., Pandini V., Vanoni M.A., Mattevi A.,
RA Coda A., Aliverti A., Zanetti G.;
RT "Role of the His57-Glu214 ionic couple located in the active site of
RT Mycobacterium tuberculosis FprA.";
RL Biochemistry 45:8712-8720(2006).
CC -!- FUNCTION: Transports electrons between ferredoxin and NADPH. May supply
CC electrons to P450 systems (PubMed:12071965). The enzyme can use both
CC NADPH and NADH as a reductant, but the catalytic efficiency is two
CC orders of magnitude higher with NADPH (PubMed:12071965).
CC {ECO:0000269|PubMed:12071965}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + NADP(+) + 2 reduced [2Fe-2S]-[ferredoxin] = NADPH + 2
CC oxidized [2Fe-2S]-[ferredoxin]; Xref=Rhea:RHEA:20125, Rhea:RHEA-
CC COMP:10000, Rhea:RHEA-COMP:10001, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=1.18.1.2;
CC Evidence={ECO:0000269|PubMed:12071965};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:12071965};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=22 uM for ferricyanide (in the presence of NADPH)
CC {ECO:0000269|PubMed:12071965};
CC KM=14.6 uM for ferricyanide (in the presence of NADH)
CC {ECO:0000269|PubMed:12071965};
CC KM=58 uM for 2,6-dichlorophenol-indophenol (in the presence of NADPH)
CC {ECO:0000269|PubMed:12071965};
CC KM=56 uM for 2,6-dichlorophenol-indophenol (in the presence of NADH)
CC {ECO:0000269|PubMed:12071965};
CC KM=0.45 uM for NADPH (in the presence of ferricyanide)
CC {ECO:0000269|PubMed:12071965};
CC KM=0.89 uM for NADPH (in the presence of 2,6-dichlorophenol-
CC indophenol) {ECO:0000269|PubMed:12071965};
CC KM=68 uM for NADH (in the presence of ferricyanide)
CC {ECO:0000269|PubMed:12071965};
CC KM=83 uM for NADH (in the presence of 2,6-dichlorophenol-indophenol)
CC {ECO:0000269|PubMed:12071965};
CC Note=kcat is 63.0 sec(-1) with ferricyanide and NADPH as substrates.
CC kcat is 25.6 sec(-1) with 2,6-dichlorophenol-indophenol and NADPH as
CC substrates. kcat is 42 sec(-1) with ferricyanide and NADH as
CC substrates. kcat is 21 sec(-1) with 2,6-dichlorophenol-indophenol and
CC NADH as substrates. {ECO:0000269|PubMed:12071965};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:12071965,
CC ECO:0000269|PubMed:12102623, ECO:0000269|PubMed:16846214}.
CC -!- SIMILARITY: Belongs to the ferredoxin--NADP reductase type 1 family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP45916.1; -; Genomic_DNA.
DR PIR; A70920; A70920.
DR RefSeq; NP_217622.1; NC_000962.3.
DR RefSeq; WP_003900632.1; NZ_NVQJ01000011.1.
DR PDB; 1LQT; X-ray; 1.05 A; A/B=1-456.
DR PDB; 1LQU; X-ray; 1.25 A; A/B=1-456.
DR PDB; 2C7G; X-ray; 1.80 A; A=1-456.
DR PDBsum; 1LQT; -.
DR PDBsum; 1LQU; -.
DR PDBsum; 2C7G; -.
DR AlphaFoldDB; P9WIQ3; -.
DR SMR; P9WIQ3; -.
DR STRING; 83332.Rv3106; -.
DR DrugBank; DB01753; 4-oxo-nicotinamide-adenine dinucleotide phosphate.
DR DrugBank; DB03147; Flavin adenine dinucleotide.
DR PaxDb; P9WIQ3; -.
DR DNASU; 888839; -.
DR GeneID; 888839; -.
DR KEGG; mtu:Rv3106; -.
DR TubercuList; Rv3106; -.
DR eggNOG; COG0493; Bacteria.
DR OMA; MRPYHVA; -.
DR PhylomeDB; P9WIQ3; -.
DR BRENDA; 1.18.1.6; 3445.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0008860; F:ferredoxin-NAD+ reductase activity; IDA:MTBBASE.
DR GO; GO:0004324; F:ferredoxin-NADP+ reductase activity; IDA:MTBBASE.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IDA:MTBBASE.
DR GO; GO:0070401; F:NADP+ binding; IDA:MTBBASE.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR023753; FAD/NAD-binding_dom.
DR InterPro; IPR021163; Ferredox_Rdtase_adrenod.
DR Pfam; PF07992; Pyr_redox_2; 1.
DR PIRSF; PIRSF000362; FNR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; FAD; Flavoprotein; NADP;
KW Oxidoreductase; Reference proteome.
FT CHAIN 1..456
FT /note="NADPH-ferredoxin reductase FprA"
FT /id="PRO_0000087329"
FT BINDING 14
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:16846214"
FT BINDING 40
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:16846214"
FT BINDING 48
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:16846214"
FT BINDING 84
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:16846214"
FT BINDING 110
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:12102623,
FT ECO:0000269|PubMed:16846214"
FT BINDING 155..158
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:12102623,
FT ECO:0000269|PubMed:16846214"
FT BINDING 199..200
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:12102623,
FT ECO:0000269|PubMed:16846214"
FT BINDING 211
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:12102623,
FT ECO:0000269|PubMed:16846214"
FT BINDING 359
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:16846214"
FT BINDING 366..368
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:16846214"
FT BINDING 366
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:12102623,
FT ECO:0000269|PubMed:16846214"
FT MUTAGEN 57
FT /note="H->A,Q: Reduces activity 4-fold."
FT MUTAGEN 214
FT /note="E->A: No effect on activity. Decreases Km for NADP
FT 2-fold."
FT STRAND 4..9
FT /evidence="ECO:0007829|PDB:1LQT"
FT HELIX 13..28
FT /evidence="ECO:0007829|PDB:1LQT"
FT STRAND 34..44
FT /evidence="ECO:0007829|PDB:1LQT"
FT HELIX 48..51
FT /evidence="ECO:0007829|PDB:1LQT"
FT HELIX 59..63
FT /evidence="ECO:0007829|PDB:1LQT"
FT HELIX 64..71
FT /evidence="ECO:0007829|PDB:1LQT"
FT STRAND 76..81
FT /evidence="ECO:0007829|PDB:1LQT"
FT TURN 84..86
FT /evidence="ECO:0007829|PDB:1LQT"
FT HELIX 90..96
FT /evidence="ECO:0007829|PDB:1LQT"
FT STRAND 97..102
FT /evidence="ECO:0007829|PDB:1LQT"
FT TURN 115..118
FT /evidence="ECO:0007829|PDB:1LQT"
FT STRAND 122..124
FT /evidence="ECO:0007829|PDB:1LQT"
FT HELIX 125..132
FT /evidence="ECO:0007829|PDB:1LQT"
FT HELIX 136..138
FT /evidence="ECO:0007829|PDB:1LQT"
FT STRAND 147..153
FT /evidence="ECO:0007829|PDB:1LQT"
FT HELIX 157..167
FT /evidence="ECO:0007829|PDB:1LQT"
FT HELIX 170..173
FT /evidence="ECO:0007829|PDB:1LQT"
FT HELIX 180..186
FT /evidence="ECO:0007829|PDB:1LQT"
FT STRAND 193..197
FT /evidence="ECO:0007829|PDB:1LQT"
FT HELIX 202..204
FT /evidence="ECO:0007829|PDB:1LQT"
FT HELIX 209..214
FT /evidence="ECO:0007829|PDB:1LQT"
FT HELIX 215..217
FT /evidence="ECO:0007829|PDB:1LQT"
FT STRAND 221..224
FT /evidence="ECO:0007829|PDB:1LQT"
FT HELIX 227..230
FT /evidence="ECO:0007829|PDB:1LQT"
FT HELIX 235..241
FT /evidence="ECO:0007829|PDB:1LQT"
FT HELIX 243..256
FT /evidence="ECO:0007829|PDB:1LQT"
FT STRAND 264..270
FT /evidence="ECO:0007829|PDB:1LQT"
FT STRAND 272..279
FT /evidence="ECO:0007829|PDB:1LQT"
FT STRAND 281..283
FT /evidence="ECO:0007829|PDB:1LQT"
FT STRAND 286..296
FT /evidence="ECO:0007829|PDB:1LQT"
FT STRAND 298..314
FT /evidence="ECO:0007829|PDB:1LQT"
FT STRAND 316..320
FT /evidence="ECO:0007829|PDB:1LQT"
FT TURN 336..339
FT /evidence="ECO:0007829|PDB:1LQT"
FT STRAND 352..356
FT /evidence="ECO:0007829|PDB:1LQT"
FT HELIX 359..362
FT /evidence="ECO:0007829|PDB:1LQT"
FT HELIX 368..370
FT /evidence="ECO:0007829|PDB:1LQT"
FT HELIX 371..391
FT /evidence="ECO:0007829|PDB:1LQT"
FT HELIX 402..413
FT /evidence="ECO:0007829|PDB:1LQT"
FT HELIX 420..434
FT /evidence="ECO:0007829|PDB:1LQT"
FT HELIX 435..437
FT /evidence="ECO:0007829|PDB:1LQT"
FT HELIX 447..454
FT /evidence="ECO:0007829|PDB:1LQT"
SQ SEQUENCE 456 AA; 49341 MW; 74D91282BD78BFB9 CRC64;
MRPYYIAIVG SGPSAFFAAA SLLKAADTTE DLDMAVDMLE MLPTPWGLVR SGVAPDHPKI
KSISKQFEKT AEDPRFRFFG NVVVGEHVQP GELSERYDAV IYAVGAQSDR MLNIPGEDLP
GSIAAVDFVG WYNAHPHFEQ VSPDLSGARA VVIGNGNVAL DVARILLTDP DVLARTDIAD
HALESLRPRG IQEVVIVGRR GPLQAAFTTL ELRELADLDG VDVVIDPAEL DGITDEDAAA
VGKVCKQNIK VLRGYADREP RPGHRRMVFR FLTSPIEIKG KRKVERIVLG RNELVSDGSG
RVAAKDTGER EELPAQLVVR SVGYRGVPTP GLPFDDQSGT IPNVGGRING SPNEYVVGWI
KRGPTGVIGT NKKDAQDTVD TLIKNLGNAK EGAECKSFPE DHADQVADWL AARQPKLVTS
AHWQVIDAFE RAAGEPHGRP RVKLASLAEL LRIGLG
