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 18-SEP-2019, entry version 35. 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., RA Harris D.E., Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, RA Tekaia F., Badcock K., Basham D., Brown D., Chillingworth T., RA Connor R., Davies R.M., Devlin K., Feltwell T., Gentles S., Hamlin N., RA Holroyd S., Hornsby T., Jagels K., Krogh A., McLean J., Moule S., RA Murphy L.D., Oliver S., Osborne J., Quail M.A., Rajandream M.A., RA Rogers J., Rutter S., Seeger K., Skelton S., Squares S., Squares R., RA Sulston J.E., Taylor K., Whitehead S., Barrell B.G.; RT "Deciphering the biology of Mycobacterium tuberculosis from the RT complete 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 RP 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., RA Yadav A.K., Shrivastava P., Marimuthu A., Anand S., Sundaram H., RA Kingsbury R., Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., RA Katoch K., Katoch V.M., Kumar P., Chaerkady R., Ramachandran S., RA Dash D., Pandey A.; RT "Proteogenomic analysis of Mycobacterium tuberculosis by high RT resolution 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 RP IN COMPLEX WITH SUBSTRATES AND SUBSTRATE ANALOGS, MUTAGENESIS OF RP SER-318, 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., RA Boshoff H.I., 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; CC EC=4.2.1.2; 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)- CC malate 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 CC A site, and the non-catalytic B site that may play a role in the CC transfer of substrate or product between the active site and the CC solvent. 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. CC Fumarase subfamily. {ECO:0000255|HAMAP-Rule:MF_00743, CC ECO:0000305}. 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; 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 PDBsum; 3NO9; -. DR PDBsum; 4ADL; -. DR PDBsum; 4ADM; -. DR PDBsum; 4APA; -. DR PDBsum; 4APB; -. DR PDBsum; 5F91; -. DR PDBsum; 5F92; -. DR SMR; P9WN93; -. DR MINT; P9WN93; -. DR STRING; 83332.Rv1098c; -. DR iPTMnet; P9WN93; -. DR PaxDb; P9WN93; -. DR PRIDE; P9WN93; -. DR EnsemblBacteria; CCP43851; CCP43851; Rv1098c. DR GeneID; 885651; -. DR KEGG; mtu:Rv1098c; -. DR KEGG; mtv:RVBD_1098c; -. DR TubercuList; Rv1098c; -. DR eggNOG; ENOG4105C9Q; Bacteria. DR eggNOG; COG0114; LUCA. DR KO; K01679; -. DR OMA; FELNVYN; -. DR PhylomeDB; P9WN93; -. DR BioCyc; MetaCyc:G185E-5263-MONOMER; -. DR BioCyc; MTBH37RV:G185E-5263-MONOMER; -. DR UniPathway; UPA00223; UER01007. DR Proteomes; UP000001584; Chromosome. DR GO; GO:0005618; C:cell wall; HDA:MTBBASE. DR GO; GO:0005829; C:cytosol; HDA:MTBBASE. DR GO; GO:0005576; C:extracellular region; 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; Complete proteome; Cytoplasm; Lyase; KW Reference proteome; Tricarboxylic acid cycle. FT INIT_MET 1 1 Removed. {ECO:0000244|PubMed:21969609}. FT CHAIN 2 474 Fumarate hydratase class II. FT /FTId=PRO_0000161289. FT REGION 104 106 Substrate binding. {ECO:0000244|PDB:4ADL, FT ECO:0000244|PDB:4ADM, FT ECO:0000244|PDB:4APB, FT ECO:0000244|PDB:5F92, ECO:0000255|HAMAP- FT Rule:MF_00743, FT ECO:0000269|PubMed:22561013, FT ECO:0000269|PubMed:27325754}. FT REGION 128 131 Substrate binding (B site). FT {ECO:0000255|HAMAP-Rule:MF_00743}. FT REGION 138 140 Substrate binding. {ECO:0000244|PDB:4ADL, FT ECO:0000244|PDB:4ADM, FT ECO:0000244|PDB:4APB, FT ECO:0000244|PDB:5F91, FT ECO:0000244|PDB:5F92, ECO:0000255|HAMAP- FT Rule:MF_00743, FT ECO:0000269|PubMed:22561013, FT ECO:0000269|PubMed:27325754}. FT REGION 324 326 Substrate binding. {ECO:0000244|PDB:4ADL, FT ECO:0000244|PDB:4ADM, FT ECO:0000244|PDB:4APB, FT ECO:0000244|PDB:5F91, FT ECO:0000244|PDB:5F92, ECO:0000255|HAMAP- FT Rule:MF_00743, FT ECO:0000269|PubMed:22561013, FT ECO:0000269|PubMed:27325754}. FT ACT_SITE 187 187 Proton donor/acceptor. FT {ECO:0000244|PDB:4ADL, FT ECO:0000244|PDB:4ADM, ECO:0000255|HAMAP- FT Rule:MF_00743, FT ECO:0000305|PubMed:22561013}. FT ACT_SITE 318 318 {ECO:0000244|PDB:4ADM, ECO:0000255|HAMAP- FT Rule:MF_00743, FT ECO:0000269|PubMed:22561013}. FT BINDING 186 186 Substrate. {ECO:0000244|PDB:4ADL, FT ECO:0000244|PDB:4APB, FT ECO:0000244|PDB:5F91, FT ECO:0000244|PDB:5F92, ECO:0000255|HAMAP- FT Rule:MF_00743, FT ECO:0000269|PubMed:22561013, FT ECO:0000269|PubMed:27325754}. FT BINDING 319 319 Substrate. {ECO:0000244|PDB:4ADL, FT ECO:0000244|PDB:4APB, FT ECO:0000244|PDB:5F92, ECO:0000255|HAMAP- FT Rule:MF_00743, FT ECO:0000269|PubMed:22561013, FT ECO:0000269|PubMed:27325754}. FT SITE 331 331 Important for catalytic activity. FT {ECO:0000255|HAMAP-Rule:MF_00743}. FT MOD_RES 2 2 N-acetylalanine. FT {ECO:0000244|PubMed:21969609}. FT MUTAGEN 318 318 S->A,C: Absence of fumarase activity. FT {ECO:0000269|PubMed:22561013}. FT STRAND 10 15 {ECO:0000244|PDB:4ADM}. FT STRAND 18 23 {ECO:0000244|PDB:4ADM}. FT HELIX 30 38 {ECO:0000244|PDB:4ADM}. FT STRAND 41 43 {ECO:0000244|PDB:4ADM}. FT HELIX 48 67 {ECO:0000244|PDB:4ADM}. FT HELIX 73 87 {ECO:0000244|PDB:4ADM}. FT TURN 89 91 {ECO:0000244|PDB:4APB}. FT HELIX 92 94 {ECO:0000244|PDB:4ADM}. FT STRAND 98 101 {ECO:0000244|PDB:4ADM}. FT HELIX 106 122 {ECO:0000244|PDB:4ADM}. FT TURN 129 136 {ECO:0000244|PDB:4ADM}. FT HELIX 139 157 {ECO:0000244|PDB:4ADM}. FT HELIX 159 176 {ECO:0000244|PDB:4ADM}. FT TURN 177 179 {ECO:0000244|PDB:4ADM}. FT STRAND 181 186 {ECO:0000244|PDB:4ADM}. FT STRAND 189 195 {ECO:0000244|PDB:4ADM}. FT HELIX 196 221 {ECO:0000244|PDB:4ADM}. FT TURN 229 231 {ECO:0000244|PDB:4ADM}. FT HELIX 241 253 {ECO:0000244|PDB:4ADM}. FT HELIX 266 269 {ECO:0000244|PDB:4ADM}. FT HELIX 272 298 {ECO:0000244|PDB:4ADM}. FT TURN 302 304 {ECO:0000244|PDB:3NO9}. FT STRAND 319 321 {ECO:0000244|PDB:4ADM}. FT HELIX 328 352 {ECO:0000244|PDB:4ADM}. FT HELIX 362 386 {ECO:0000244|PDB:4ADM}. FT HELIX 388 390 {ECO:0000244|PDB:4ADM}. FT HELIX 395 404 {ECO:0000244|PDB:4ADM}. FT HELIX 406 412 {ECO:0000244|PDB:4ADM}. FT HELIX 413 416 {ECO:0000244|PDB:4ADM}. FT HELIX 418 431 {ECO:0000244|PDB:4ADM}. FT HELIX 435 441 {ECO:0000244|PDB:4ADM}. FT STRAND 446 448 {ECO:0000244|PDB:4APB}. FT HELIX 451 457 {ECO:0000244|PDB:4ADM}. FT HELIX 460 463 {ECO:0000244|PDB:4ADM}. 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 //