DITCY_MYCTU
ID DITCY_MYCTU Reviewed; 501 AA.
AC O50406; F2GEC3; L0TCC7;
DT 11-JUL-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Type B diterpene cyclase;
DE EC=5.5.1.16;
GN OrderedLocusNames=Rv3377c;
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 FUNCTION AS A DITERPENE CYCLASE AND IN TUBERCULOSINOL BIOSYNTHESIS,
RP CATALYTIC ACTIVITY, AND NOMENCLATURE.
RX PubMed=15719101; DOI=10.1039/b415346d;
RA Nakano C., Okamura T., Sato T., Dairi T., Hoshino T.;
RT "Mycobacterium tuberculosis H37Rv3377c encodes the diterpene cyclase for
RT producing the halimane skeleton.";
RL Chem. Commun. (Camb.) 8:1016-1018(2005).
RN [3]
RP FUNCTION AS A DITERPENE CYCLASE, CATALYTIC ACTIVITY, MUTAGENESIS OF
RP GLU-292; ASP-293; ASP-295; THR-296 AND THR-297, SUBSTRATE SPECIFICITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, SUBUNIT, AND ACTIVITY REGULATION.
RX PubMed=19618417; DOI=10.1002/cbic.200900248;
RA Nakano C., Hoshino T.;
RT "Characterization of the Rv3377c gene product, a type-B diterpene cyclase,
RT from the Mycobacterium tuberculosis H37 genome.";
RL ChemBioChem 10:2060-2071(2009).
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).
CC -!- FUNCTION: Catalyzes the formation of tuberculosinyl diphosphate from
CC geranylgeranyl diphosphate (GGPP). It could also react with (14R/S)-
CC 14,15-oxidoGGPP to generate 3alpha- and 3beta-hydroxytuberculosinyl
CC diphosphate. {ECO:0000269|PubMed:15719101,
CC ECO:0000269|PubMed:19618417}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=geranylgeranyl diphosphate = tuberculosinyl diphosphate;
CC Xref=Rhea:RHEA:25621, ChEBI:CHEBI:57533, ChEBI:CHEBI:58822;
CC EC=5.5.1.16; Evidence={ECO:0000269|PubMed:15719101,
CC ECO:0000269|PubMed:19618417};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:19618417};
CC -!- ACTIVITY REGULATION: Strongly inhibited by 15-aza-
CC dihydrogeranylgeraniol and 5-isopropyl-N,N,N,2-tetramethyl-4-
CC (piperidine-1-carbonyloxy)benzenaminium chloride (Amo-1618). Inhibited
CC by GGPP concentrations higher than 50 uM.
CC {ECO:0000269|PubMed:19618417}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=11.7 uM for GGPP (at 30 degrees Celsius and pH 7.5)
CC {ECO:0000269|PubMed:19618417};
CC Vmax=186 nmol/min/mg enzyme (at 30 degrees Celsius and pH 7.5)
CC {ECO:0000269|PubMed:19618417};
CC pH dependence:
CC Optimum pH is 7.5. Enzyme activity is not detected at pH values above
CC 9.0. {ECO:0000269|PubMed:19618417};
CC Temperature dependence:
CC Optimum temperature is 30 degrees Celsius.
CC {ECO:0000269|PubMed:19618417};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:19618417}.
CC -!- SIMILARITY: Belongs to the terpene synthase family. {ECO:0000305}.
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DR EMBL; AL123456; CCP46198.1; -; Genomic_DNA.
DR PIR; H70972; H70972.
DR RefSeq; NP_217894.1; NC_000962.3.
DR RefSeq; WP_003417905.1; NZ_NVQJ01000052.1.
DR PDB; 6VPT; X-ray; 2.72 A; A=1-501.
DR PDBsum; 6VPT; -.
DR AlphaFoldDB; O50406; -.
DR SMR; O50406; -.
DR STRING; 83332.Rv3377c; -.
DR SwissLipids; SLP:000001170; -.
DR PaxDb; O50406; -.
DR DNASU; 888073; -.
DR GeneID; 888073; -.
DR KEGG; mtu:Rv3377c; -.
DR TubercuList; Rv3377c; -.
DR eggNOG; COG1657; Bacteria.
DR InParanoid; O50406; -.
DR OMA; RWHASPY; -.
DR PhylomeDB; O50406; -.
DR BioCyc; MetaCyc:G185E-7653-MON; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0035439; F:halimadienyl-diphosphate synthase activity; IDA:MTBBASE.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0000287; F:magnesium ion binding; IDA:MTBBASE.
DR GO; GO:0010350; P:cellular response to magnesium starvation; IDA:MTBBASE.
DR GO; GO:0033385; P:geranylgeranyl diphosphate metabolic process; IDA:MTBBASE.
DR GO; GO:0052572; P:response to host immune response; IMP:MTBBASE.
DR GO; GO:0035440; P:tuberculosinol biosynthetic process; IDA:MTBBASE.
DR InterPro; IPR001330; PFTB_repeat.
DR InterPro; IPR032696; SQ_cyclase_C.
DR InterPro; IPR008930; Terpenoid_cyclase/PrenylTrfase.
DR Pfam; PF00432; Prenyltrans; 1.
DR Pfam; PF13243; SQHop_cyclase_C; 1.
DR SUPFAM; SSF48239; SSF48239; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Isomerase; Lyase; Magnesium; Metal-binding;
KW Reference proteome.
FT CHAIN 1..501
FT /note="Type B diterpene cyclase"
FT /id="PRO_0000416457"
FT MUTAGEN 292
FT /note="E->Q: No change."
FT /evidence="ECO:0000269|PubMed:19618417"
FT MUTAGEN 293
FT /note="D->E: Loss of cyclase activity."
FT /evidence="ECO:0000269|PubMed:19618417"
FT MUTAGEN 293
FT /note="D->N: Loss of cyclase activity."
FT /evidence="ECO:0000269|PubMed:19618417"
FT MUTAGEN 295
FT /note="D->N: Loss of cyclase activity."
FT /evidence="ECO:0000269|PubMed:19618417"
FT MUTAGEN 295
FT /note="D->Q: Loss of cyclase activity."
FT /evidence="ECO:0000269|PubMed:19618417"
FT MUTAGEN 296
FT /note="T->D: Loss of cyclase activity."
FT /evidence="ECO:0000269|PubMed:19618417"
FT MUTAGEN 296
FT /note="T->N: Loss of cyclase activity."
FT /evidence="ECO:0000269|PubMed:19618417"
FT MUTAGEN 296
FT /note="T->S: Loss of cyclase activity."
FT /evidence="ECO:0000269|PubMed:19618417"
FT MUTAGEN 296
FT /note="T->V: Loss of cyclase activity."
FT /evidence="ECO:0000269|PubMed:19618417"
FT MUTAGEN 297
FT /note="T->S: Loss of cyclase activity."
FT /evidence="ECO:0000269|PubMed:19618417"
FT MUTAGEN 297
FT /note="T->V: Loss of cyclase activity."
FT /evidence="ECO:0000269|PubMed:19618417"
FT HELIX 4..11
FT /evidence="ECO:0007829|PDB:6VPT"
FT HELIX 21..27
FT /evidence="ECO:0007829|PDB:6VPT"
FT HELIX 28..30
FT /evidence="ECO:0007829|PDB:6VPT"
FT TURN 31..33
FT /evidence="ECO:0007829|PDB:6VPT"
FT HELIX 35..47
FT /evidence="ECO:0007829|PDB:6VPT"
FT STRAND 58..60
FT /evidence="ECO:0007829|PDB:6VPT"
FT HELIX 63..79
FT /evidence="ECO:0007829|PDB:6VPT"
FT HELIX 83..86
FT /evidence="ECO:0007829|PDB:6VPT"
FT HELIX 87..101
FT /evidence="ECO:0007829|PDB:6VPT"
FT HELIX 119..132
FT /evidence="ECO:0007829|PDB:6VPT"
FT HELIX 147..155
FT /evidence="ECO:0007829|PDB:6VPT"
FT HELIX 156..158
FT /evidence="ECO:0007829|PDB:6VPT"
FT HELIX 168..176
FT /evidence="ECO:0007829|PDB:6VPT"
FT HELIX 181..183
FT /evidence="ECO:0007829|PDB:6VPT"
FT HELIX 200..209
FT /evidence="ECO:0007829|PDB:6VPT"
FT HELIX 215..227
FT /evidence="ECO:0007829|PDB:6VPT"
FT STRAND 232..236
FT /evidence="ECO:0007829|PDB:6VPT"
FT HELIX 239..250
FT /evidence="ECO:0007829|PDB:6VPT"
FT HELIX 260..275
FT /evidence="ECO:0007829|PDB:6VPT"
FT TURN 279..281
FT /evidence="ECO:0007829|PDB:6VPT"
FT HELIX 294..306
FT /evidence="ECO:0007829|PDB:6VPT"
FT HELIX 314..317
FT /evidence="ECO:0007829|PDB:6VPT"
FT STRAND 322..325
FT /evidence="ECO:0007829|PDB:6VPT"
FT HELIX 336..348
FT /evidence="ECO:0007829|PDB:6VPT"
FT HELIX 356..367
FT /evidence="ECO:0007829|PDB:6VPT"
FT STRAND 371..374
FT /evidence="ECO:0007829|PDB:6VPT"
FT STRAND 379..382
FT /evidence="ECO:0007829|PDB:6VPT"
FT HELIX 384..395
FT /evidence="ECO:0007829|PDB:6VPT"
FT TURN 396..398
FT /evidence="ECO:0007829|PDB:6VPT"
FT HELIX 400..412
FT /evidence="ECO:0007829|PDB:6VPT"
FT HELIX 429..446
FT /evidence="ECO:0007829|PDB:6VPT"
FT HELIX 451..461
FT /evidence="ECO:0007829|PDB:6VPT"
FT STRAND 473..479
FT /evidence="ECO:0007829|PDB:6VPT"
FT HELIX 482..498
FT /evidence="ECO:0007829|PDB:6VPT"
SQ SEQUENCE 501 AA; 55262 MW; B9B6076F13837AFE CRC64;
METFRTLLAK AALGNGISST AYDTAWVAKL GQLDDELSDL ALNWLCERQL PDGSWGAEFP
FCYEDRLLST LAAMISLTSN KHRRRRAAQV EKGLLALKNL TSGAFEGPQL DIKDATVGFE
LIAPTLMAEA ARLGLAICHE ESILGELVGV REQKLRKLGG SKINKHITAA FSVELAGQDG
VGMLDVDNLQ ETNGSVKYSP SASAYFALHV KPGDKRALAY ISSIIQAGDG GAPAFYQAEI
FEIVWSLWNL SRTDIDLSDP EIVRTYLPYL DHVEQHWVRG RGVGWTGNST LEDCDTTSVA
YDVLSKFGRS PDIGAVLQFE DADWFRTYFH EVGPSISTNV HVLGALKQAG YDKCHPRVRK
VLEFIRSSKE PGRFCWRDKW HRSAYYTTAH LICAASNYDD ALCSDAIGWI LNTQRPDGSW
GFFDGQATAE ETAYCIQALA HWQRHSGTSL SAQISRAGGW LSQHCEPPYA PLWIAKTLYC
SATVVKAAIL SALRLVDESN Q
