FUMC_MYCTU
ID FUMC_MYCTU Reviewed; 474 AA.
AC P9WN93; L0T5U4; O53446;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 49.
DE RecName: Full=Fumarate hydratase class II {ECO:0000255|HAMAP-Rule:MF_00743, ECO:0000303|PubMed:22561013};
DE Short=Fumarase C {ECO:0000255|HAMAP-Rule:MF_00743, ECO:0000303|PubMed:22561013};
DE EC=4.2.1.2 {ECO:0000255|HAMAP-Rule:MF_00743, ECO:0000305|PubMed:27325754};
DE AltName: Full=Aerobic fumarase {ECO:0000255|HAMAP-Rule:MF_00743};
DE AltName: Full=Iron-independent fumarase {ECO:0000255|HAMAP-Rule:MF_00743};
GN Name=fumC {ECO:0000255|HAMAP-Rule:MF_00743}; Synonyms=fum;
GN OrderedLocusNames=Rv1098c; ORFNames=MTV017.51c;
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 ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-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 [3]
RP X-RAY CRYSTALLOGRAPHY (2.48 ANGSTROMS), AND SUBUNIT.
RG Mycobacterium tuberculosis structural genomics consortium (TB);
RT "Crystal structure of apo fumarate hydratase from Mycobacterium
RT tuberculosis.";
RL Submitted (JUL-2010) to the PDB data bank.
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF MUTANTS ALA-318 AND CYS-318 IN
RP COMPLEX WITH SUBSTRATES AND SUBSTRATE ANALOGS, MUTAGENESIS OF SER-318,
RP ACTIVE SITE, REACTION MECHANISM, AND SUBUNIT.
RX PubMed=22561013; DOI=10.1016/j.febslet.2012.04.034;
RA Mechaly A.E., Haouz A., Miras I., Barilone N., Weber P., Shepard W.,
RA Alzari P.M., Bellinzoni M.;
RT "Conformational changes upon ligand binding in the essential class II
RT fumarase Rv1098c from Mycobacterium tuberculosis.";
RL FEBS Lett. 586:1606-1611(2012).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS) IN COMPLEX WITH SUBSTRATE AND
RP SUBSTRATE ANALOGS, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, ACTIVITY REGULATION, AND SUBUNIT.
RX PubMed=27325754; DOI=10.1073/pnas.1600630113;
RA Kasbekar M., Fischer G., Mott B.T., Yasgar A., Hyvoenen M., Boshoff H.I.,
RA Abell C., Barry C.E. III, Thomas C.J.;
RT "Selective small molecule inhibitor of the Mycobacterium tuberculosis
RT fumarate hydratase reveals an allosteric regulatory site.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:7503-7508(2016).
CC -!- FUNCTION: Involved in the TCA cycle. Catalyzes the stereospecific
CC interconversion of fumarate to L-malate. {ECO:0000255|HAMAP-
CC Rule:MF_00743, ECO:0000305|PubMed:27325754}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-malate = fumarate + H2O; Xref=Rhea:RHEA:12460,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15589, ChEBI:CHEBI:29806; EC=4.2.1.2;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00743,
CC ECO:0000305|PubMed:27325754};
CC -!- ACTIVITY REGULATION: Competitively inhibited by N-(5-(azepan-1-
CC ylsulfonyl)-2-methoxyphenyl)- 2-(4-oxo-3,4-dihydrophthalazin-1-
CC yl)acetamide. {ECO:0000269|PubMed:27325754}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=260 uM for fumarate {ECO:0000269|PubMed:27325754};
CC -!- PATHWAY: Carbohydrate metabolism; tricarboxylic acid cycle; (S)-malate
CC from fumarate: step 1/1. {ECO:0000255|HAMAP-Rule:MF_00743,
CC ECO:0000305}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000255|HAMAP-Rule:MF_00743,
CC ECO:0000269|PubMed:22561013, ECO:0000269|PubMed:27325754,
CC ECO:0000269|Ref.3}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00743,
CC ECO:0000305}.
CC -!- MISCELLANEOUS: There are 2 substrate-binding sites: the catalytic A
CC site, and the non-catalytic B site that may play a role in the transfer
CC of substrate or product between the active site and the solvent.
CC Alternatively, the B site may bind allosteric effectors.
CC {ECO:0000255|HAMAP-Rule:MF_00743}.
CC -!- SIMILARITY: Belongs to the class-II fumarase/aspartase family. Fumarase
CC subfamily. {ECO:0000255|HAMAP-Rule:MF_00743, ECO:0000305}.
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DR EMBL; AL123456; CCP43851.1; -; Genomic_DNA.
DR PIR; H70896; H70896.
DR RefSeq; NP_215614.1; NC_000962.3.
DR RefSeq; WP_003405805.1; NZ_NVQJ01000021.1.
DR PDB; 3NO9; X-ray; 2.48 A; A/B/C/D=1-474.
DR PDB; 4ADL; X-ray; 2.20 A; A/B/C/D=1-473.
DR PDB; 4ADM; X-ray; 1.65 A; A/B/C/D=1-473.
DR PDB; 4APA; X-ray; 2.04 A; A/B/C/D=2-474.
DR PDB; 4APB; X-ray; 1.94 A; A/B/C/D=2-474.
DR PDB; 5F91; X-ray; 2.00 A; A/B/C/D=2-474.
DR PDB; 5F92; X-ray; 1.86 A; A/B/C/D=2-474.
DR PDB; 6S43; X-ray; 1.42 A; A/B/C/D=1-474.
DR PDB; 6S7K; X-ray; 1.55 A; A/B/C/D=1-474.
DR PDB; 6S7S; X-ray; 1.70 A; A/B/C/D=1-474.
DR PDB; 6S7U; X-ray; 1.48 A; A/B/C/D=1-474.
DR PDB; 6S7W; X-ray; 1.44 A; A/B/C/D=1-474.
DR PDB; 6S7Z; X-ray; 1.85 A; A/B/C/D=1-474.
DR PDB; 6S88; X-ray; 1.59 A; A/B/C/D=1-474.
DR PDBsum; 3NO9; -.
DR PDBsum; 4ADL; -.
DR PDBsum; 4ADM; -.
DR PDBsum; 4APA; -.
DR PDBsum; 4APB; -.
DR PDBsum; 5F91; -.
DR PDBsum; 5F92; -.
DR PDBsum; 6S43; -.
DR PDBsum; 6S7K; -.
DR PDBsum; 6S7S; -.
DR PDBsum; 6S7U; -.
DR PDBsum; 6S7W; -.
DR PDBsum; 6S7Z; -.
DR PDBsum; 6S88; -.
DR AlphaFoldDB; P9WN93; -.
DR SMR; P9WN93; -.
DR MINT; P9WN93; -.
DR STRING; 83332.Rv1098c; -.
DR iPTMnet; P9WN93; -.
DR PaxDb; P9WN93; -.
DR DNASU; 885651; -.
DR GeneID; 885651; -.
DR KEGG; mtu:Rv1098c; -.
DR TubercuList; Rv1098c; -.
DR eggNOG; COG0114; Bacteria.
DR OMA; HDSMGEV; -.
DR PhylomeDB; P9WN93; -.
DR BioCyc; MetaCyc:G185E-5263-MON; -.
DR BRENDA; 4.2.1.2; 3445.
DR SABIO-RK; P9WN93; -.
DR UniPathway; UPA00223; UER01007.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR GO; GO:0005576; C:extracellular region; HDA:MTBBASE.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0045239; C:tricarboxylic acid cycle enzyme complex; IEA:InterPro.
DR GO; GO:0004333; F:fumarate hydratase activity; IDA:UniProtKB.
DR GO; GO:0006106; P:fumarate metabolic process; IEA:InterPro.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-UniRule.
DR CDD; cd01362; Fumarase_classII; 1.
DR Gene3D; 1.10.275.10; -; 1.
DR HAMAP; MF_00743; FumaraseC; 1.
DR InterPro; IPR005677; Fum_hydII.
DR InterPro; IPR024083; Fumarase/histidase_N.
DR InterPro; IPR018951; Fumarase_C_C.
DR InterPro; IPR020557; Fumarate_lyase_CS.
DR InterPro; IPR000362; Fumarate_lyase_fam.
DR InterPro; IPR022761; Fumarate_lyase_N.
DR InterPro; IPR008948; L-Aspartase-like.
DR PANTHER; PTHR11444; PTHR11444; 1.
DR Pfam; PF10415; FumaraseC_C; 1.
DR Pfam; PF00206; Lyase_1; 1.
DR PRINTS; PR00149; FUMRATELYASE.
DR SUPFAM; SSF48557; SSF48557; 1.
DR PROSITE; PS00163; FUMARATE_LYASES; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Lyase; Reference proteome;
KW Tricarboxylic acid cycle.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:21969609"
FT CHAIN 2..474
FT /note="Fumarate hydratase class II"
FT /id="PRO_0000161289"
FT ACT_SITE 187
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00743,
FT ECO:0000305|PubMed:22561013, ECO:0007744|PDB:4ADL,
FT ECO:0007744|PDB:4ADM"
FT ACT_SITE 318
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00743,
FT ECO:0000269|PubMed:22561013, ECO:0007744|PDB:4ADM"
FT BINDING 104..106
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00743,
FT ECO:0000269|PubMed:22561013, ECO:0000269|PubMed:27325754,
FT ECO:0007744|PDB:4ADL, ECO:0007744|PDB:4ADM,
FT ECO:0007744|PDB:4APB, ECO:0007744|PDB:5F92"
FT BINDING 128..131
FT /ligand="substrate"
FT /note="in site B"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00743"
FT BINDING 138..140
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00743,
FT ECO:0000269|PubMed:22561013, ECO:0000269|PubMed:27325754,
FT ECO:0007744|PDB:4ADL, ECO:0007744|PDB:4ADM,
FT ECO:0007744|PDB:4APB, ECO:0007744|PDB:5F91,
FT ECO:0007744|PDB:5F92"
FT BINDING 186
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00743,
FT ECO:0000269|PubMed:22561013, ECO:0000269|PubMed:27325754,
FT ECO:0007744|PDB:4ADL, ECO:0007744|PDB:4APB,
FT ECO:0007744|PDB:5F91, ECO:0007744|PDB:5F92"
FT BINDING 319
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00743,
FT ECO:0000269|PubMed:22561013, ECO:0000269|PubMed:27325754,
FT ECO:0007744|PDB:4ADL, ECO:0007744|PDB:4APB,
FT ECO:0007744|PDB:5F92"
FT BINDING 324..326
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00743,
FT ECO:0000269|PubMed:22561013, ECO:0000269|PubMed:27325754,
FT ECO:0007744|PDB:4ADL, ECO:0007744|PDB:4ADM,
FT ECO:0007744|PDB:4APB, ECO:0007744|PDB:5F91,
FT ECO:0007744|PDB:5F92"
FT SITE 331
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00743"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:21969609"
FT MUTAGEN 318
FT /note="S->A,C: Absence of fumarase activity."
FT /evidence="ECO:0000269|PubMed:22561013"
FT STRAND 12..15
FT /evidence="ECO:0007829|PDB:6S43"
FT STRAND 18..21
FT /evidence="ECO:0007829|PDB:6S43"
FT HELIX 30..38
FT /evidence="ECO:0007829|PDB:6S43"
FT STRAND 41..43
FT /evidence="ECO:0007829|PDB:6S43"
FT HELIX 48..67
FT /evidence="ECO:0007829|PDB:6S43"
FT HELIX 73..87
FT /evidence="ECO:0007829|PDB:6S43"
FT TURN 88..91
FT /evidence="ECO:0007829|PDB:6S43"
FT HELIX 92..94
FT /evidence="ECO:0007829|PDB:6S43"
FT STRAND 99..101
FT /evidence="ECO:0007829|PDB:6S43"
FT HELIX 106..122
FT /evidence="ECO:0007829|PDB:6S43"
FT HELIX 129..133
FT /evidence="ECO:0007829|PDB:6S43"
FT TURN 134..136
FT /evidence="ECO:0007829|PDB:6S43"
FT TURN 139..141
FT /evidence="ECO:0007829|PDB:6S43"
FT HELIX 142..157
FT /evidence="ECO:0007829|PDB:6S43"
FT HELIX 159..176
FT /evidence="ECO:0007829|PDB:6S43"
FT TURN 177..179
FT /evidence="ECO:0007829|PDB:6S43"
FT STRAND 181..186
FT /evidence="ECO:0007829|PDB:6S43"
FT STRAND 189..195
FT /evidence="ECO:0007829|PDB:6S43"
FT HELIX 196..221
FT /evidence="ECO:0007829|PDB:6S43"
FT TURN 229..231
FT /evidence="ECO:0007829|PDB:6S43"
FT HELIX 241..253
FT /evidence="ECO:0007829|PDB:6S43"
FT HELIX 266..269
FT /evidence="ECO:0007829|PDB:6S43"
FT HELIX 272..298
FT /evidence="ECO:0007829|PDB:6S43"
FT STRAND 302..305
FT /evidence="ECO:0007829|PDB:6S43"
FT STRAND 308..310
FT /evidence="ECO:0007829|PDB:6S7Z"
FT STRAND 319..321
FT /evidence="ECO:0007829|PDB:6S43"
FT HELIX 328..352
FT /evidence="ECO:0007829|PDB:6S43"
FT HELIX 362..386
FT /evidence="ECO:0007829|PDB:6S43"
FT TURN 387..390
FT /evidence="ECO:0007829|PDB:6S43"
FT HELIX 395..402
FT /evidence="ECO:0007829|PDB:6S43"
FT HELIX 406..408
FT /evidence="ECO:0007829|PDB:6S43"
FT HELIX 410..412
FT /evidence="ECO:0007829|PDB:6S43"
FT HELIX 413..416
FT /evidence="ECO:0007829|PDB:6S43"
FT HELIX 418..431
FT /evidence="ECO:0007829|PDB:6S43"
FT HELIX 435..441
FT /evidence="ECO:0007829|PDB:6S43"
FT STRAND 446..448
FT /evidence="ECO:0007829|PDB:6S43"
FT HELIX 451..457
FT /evidence="ECO:0007829|PDB:6S43"
FT HELIX 460..464
FT /evidence="ECO:0007829|PDB:6S43"
SQ SEQUENCE 474 AA; 50141 MW; 4052F93F963D3DBB CRC64;
MAVDADSANY RIEHDTMGEV RVPAKALWRA QTQRAVENFP ISGRGLERTQ IRALGLLKGA
CAQVNSDLGL LAPEKADAII AAAAEIADGQ HDDQFPIDVF QTGSGTSSNM NTNEVIASIA
AKGGVTLHPN DDVNMSQSSN DTFPTATHIA ATEAAVAHLI PALQQLHDAL AAKALDWHTV
VKSGRTHLMD AVPVTLGQEF SGYARQIEAG IERVRACLPR LGELAIGGTA VGTGLNAPDD
FGVRVVAVLV AQTGLSELRT AANSFEAQAA RDGLVEASGA LRTIAVSLTK IANDIRWMGS
GPLTGLAEIQ LPDLQPGSSI MPGKVNPVLP EAVTQVAAQV IGNDAAIAWG GANGAFELNV
YIPMMARNIL ESFKLLTNVS RLFAQRCIAG LTANVEHLRR LAESSPSIVT PLNSAIGYEE
AAAVAKQALK ERKTIRQTVI DRGLIGDRLS IEDLDRRLDV LAMAKAEQLD SDRL
