PHM7_PYRSX
ID PHM7_PYRSX Reviewed; 386 AA.
AC A0A2Z5XAU0;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 10-OCT-2018, sequence version 1.
DT 03-AUG-2022, entry version 9.
DE RecName: Full=Diels-Alderase phm7 {ECO:0000303|PubMed:29972614};
DE EC=5.5.1.- {ECO:0000269|PubMed:29972614, ECO:0000269|PubMed:34121297};
DE AltName: Full=Phomasetin biosynthesis cluster protein 7 {ECO:0000303|PubMed:29972614};
GN Name=phm7 {ECO:0000303|PubMed:29972614};
OS Pyrenochaetopsis sp.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC Pleosporomycetidae; Pleosporales; Pleosporineae; Pyrenochaetopsidaceae;
OC Pyrenochaetopsis; unclassified Pyrenochaetopsis.
OX NCBI_TaxID=1756125;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, DISRUPTION
RP PHENOTYPE, AND PATHWAY.
RC STRAIN=RK10-F058;
RX PubMed=29972614; DOI=10.1002/anie.201805050;
RA Kato N., Nogawa T., Takita R., Kinugasa K., Kanai M., Uchiyama M.,
RA Osada H., Takahashi S.;
RT "Control of the stereochemical course of [4+2] cycloaddition during trans-
RT decalin formation by Fsa2-family enzymes.";
RL Angew. Chem. Int. Ed. 57:9754-9758(2018).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (1.61 ANGSTROMS) IN COMPLEX WITH INHIBITOR, DOMAIN,
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND MUTAGENESIS OF
RP LEU-49; GLU-51; ASP-53; SER-66; TYR-68; GLU-82; ASN-84; TYR-178; TRP-223;
RP LEU-245; THR-247; TRP-342; LYS-356 AND LEU-381.
RX PubMed=34121297; DOI=10.1002/anie.202106186;
RA Fujiyama K., Kato N., Re S., Kinugasa K., Watanabe K., Takita R.,
RA Nogawa T., Hino T., Osada H., Sugita Y., Takahashi S., Nagano S.;
RT "Molecular basis for two stereoselective Diels-Alderases that produce
RT decalin skeletons*.";
RL Angew. Chem. Int. Ed. 60:22401-22410(2021).
CC -!- FUNCTION: Diels-Alderase; part of the gene cluster that mediates the
CC biosynthesis of the trans-fused decalin-containing tetramic acid
CC phomasetin, the stereochemical opposite of the HIV-1 integrase
CC inhibitor equisetin (PubMed:29972614). The PKS module of phm1 together
CC with the enoylreductase phm4 catalyze the formation of the polyketide
CC unit which is then conjugated to L-serine by the condensation domain of
CC the phm1 NRPS module (PubMed:29972614). Activity of the Dieckmann
CC cyclase domain (RED) of phm1 results in release of the Dieckmann
CC product intermediate (PubMed:29972614). The Diels-Alderase phm7 then
CC uses the Dieckmann product of phm1 as substrate and catalyzes the
CC Diels-Alder cycloaddition to form the decalin ring of N-
CC desmethylphomasetin (PubMed:29972614, PubMed:34121297). N-
CC desmethylphomasetin is further methylated to phomasetin by the
CC methyltransferase phm5 (PubMed:29972614). {ECO:0000269|PubMed:29972614,
CC ECO:0000269|PubMed:34121297}.
CC -!- ACTIVITY REGULATION: 3-aminomethyl-p-menthane which is similar to the
CC phomasetin substructure, dose-dependently inhibits phm7 activity in
CC vitro and production of phomasetin in the fungus.
CC {ECO:0000269|PubMed:34121297}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:29972614}.
CC -!- DISRUPTION PHENOTYPE: Leads to a significant decrease in the production
CC of phomasetin. {ECO:0000269|PubMed:29972614}.
CC -!- SIMILARITY: Belongs to the Diels-Alderase family. {ECO:0000305}.
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DR EMBL; LC361337; BBC43190.1; -; Genomic_DNA.
DR PDB; 7DMO; X-ray; 2.00 A; A/B/C/D/E/F=1-386.
DR PDB; 7E5U; X-ray; 1.62 A; A/B/C=1-386.
DR PDB; 7E5V; X-ray; 1.61 A; A/B/C=1-386.
DR PDBsum; 7DMO; -.
DR PDBsum; 7E5U; -.
DR PDBsum; 7E5V; -.
DR SMR; A0A2Z5XAU0; -.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
PE 1: Evidence at protein level;
KW 3D-structure; Isomerase.
FT CHAIN 1..386
FT /note="Diels-Alderase phm7"
FT /id="PRO_0000453342"
FT REGION 1..223
FT /note="Beta-sandwich motif"
FT /evidence="ECO:0000305|PubMed:34121297"
FT REGION 223..386
FT /note="Beta-barrel motif"
FT /evidence="ECO:0000305|PubMed:34121297"
FT BINDING 51
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:34121297"
FT BINDING 84
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:34121297"
FT BINDING 356
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:34121297"
FT MUTAGEN 49
FT /note="L->A: Significantly decreases enzyme activity."
FT /evidence="ECO:0000269|PubMed:34121297"
FT MUTAGEN 51
FT /note="E->A: Significantly decreases enzyme activity."
FT /evidence="ECO:0000269|PubMed:34121297"
FT MUTAGEN 53
FT /note="D->A: Significantly decreases enzyme activity."
FT /evidence="ECO:0000269|PubMed:34121297"
FT MUTAGEN 66
FT /note="S->A: Significantly decreases enzyme activity."
FT /evidence="ECO:0000269|PubMed:34121297"
FT MUTAGEN 68
FT /note="Y->A: Significantly decreases enzyme activity."
FT /evidence="ECO:0000269|PubMed:34121297"
FT MUTAGEN 82
FT /note="E->A: Significantly decreases enzyme activity."
FT /evidence="ECO:0000269|PubMed:34121297"
FT MUTAGEN 84
FT /note="N->A: Significantly decreases enzyme activity."
FT /evidence="ECO:0000269|PubMed:34121297"
FT MUTAGEN 178
FT /note="Y->A: Significantly decreases enzyme activity."
FT /evidence="ECO:0000269|PubMed:34121297"
FT MUTAGEN 223
FT /note="W->A: Significantly decreases enzyme activity."
FT /evidence="ECO:0000269|PubMed:34121297"
FT MUTAGEN 245
FT /note="L->A: Significantly decreases enzyme activity."
FT /evidence="ECO:0000269|PubMed:34121297"
FT MUTAGEN 247
FT /note="T->A: Significantly decreases enzyme activity."
FT /evidence="ECO:0000269|PubMed:34121297"
FT MUTAGEN 342
FT /note="W->A: Significantly decreases enzyme activity."
FT /evidence="ECO:0000269|PubMed:34121297"
FT MUTAGEN 356
FT /note="K->A: Significantly decreases enzyme activity."
FT /evidence="ECO:0000269|PubMed:34121297"
FT MUTAGEN 381
FT /note="L->A: Significantly decreases enzyme activity."
FT /evidence="ECO:0000269|PubMed:34121297"
FT STRAND 6..15
FT /evidence="ECO:0007829|PDB:7E5V"
FT STRAND 17..20
FT /evidence="ECO:0007829|PDB:7E5V"
FT STRAND 42..45
FT /evidence="ECO:0007829|PDB:7E5U"
FT STRAND 47..55
FT /evidence="ECO:0007829|PDB:7E5V"
FT STRAND 62..71
FT /evidence="ECO:0007829|PDB:7E5V"
FT HELIX 74..76
FT /evidence="ECO:0007829|PDB:7E5V"
FT STRAND 78..86
FT /evidence="ECO:0007829|PDB:7E5V"
FT STRAND 92..106
FT /evidence="ECO:0007829|PDB:7E5V"
FT STRAND 112..117
FT /evidence="ECO:0007829|PDB:7E5V"
FT STRAND 123..128
FT /evidence="ECO:0007829|PDB:7E5V"
FT STRAND 132..141
FT /evidence="ECO:0007829|PDB:7E5V"
FT TURN 142..144
FT /evidence="ECO:0007829|PDB:7E5V"
FT STRAND 145..152
FT /evidence="ECO:0007829|PDB:7E5V"
FT HELIX 159..162
FT /evidence="ECO:0007829|PDB:7E5V"
FT HELIX 167..170
FT /evidence="ECO:0007829|PDB:7E5V"
FT STRAND 171..173
FT /evidence="ECO:0007829|PDB:7E5V"
FT STRAND 176..179
FT /evidence="ECO:0007829|PDB:7E5V"
FT STRAND 186..196
FT /evidence="ECO:0007829|PDB:7E5V"
FT TURN 197..200
FT /evidence="ECO:0007829|PDB:7E5V"
FT STRAND 201..221
FT /evidence="ECO:0007829|PDB:7E5V"
FT HELIX 223..225
FT /evidence="ECO:0007829|PDB:7E5V"
FT STRAND 228..237
FT /evidence="ECO:0007829|PDB:7E5V"
FT STRAND 240..248
FT /evidence="ECO:0007829|PDB:7E5V"
FT HELIX 251..253
FT /evidence="ECO:0007829|PDB:7E5V"
FT STRAND 258..265
FT /evidence="ECO:0007829|PDB:7E5V"
FT STRAND 268..276
FT /evidence="ECO:0007829|PDB:7E5V"
FT STRAND 291..298
FT /evidence="ECO:0007829|PDB:7E5V"
FT TURN 300..302
FT /evidence="ECO:0007829|PDB:7E5V"
FT STRAND 310..312
FT /evidence="ECO:0007829|PDB:7E5V"
FT STRAND 317..323
FT /evidence="ECO:0007829|PDB:7E5V"
FT STRAND 331..347
FT /evidence="ECO:0007829|PDB:7E5V"
FT STRAND 355..367
FT /evidence="ECO:0007829|PDB:7E5V"
FT STRAND 372..382
FT /evidence="ECO:0007829|PDB:7E5V"
SQ SEQUENCE 386 AA; 41434 MW; AE1CDA6C3E85168B CRC64;
MSEPTSSSSL DITSNCIIET PLQPSDFLPK SANLFPKFPE RISVDSWELW EFDTFDTNGS
VAFGCSLYRD ARGVEQGGFH AEVNALWPDG THWGETLYFA VSEVVENSDG TTGGKWLSKD
GGSITFHIAS DYTAAALDFN VPGKVSGTME LRNHANVSPT SNLPASDAEA QLCPGVYYTF
PMGPVATSVT ATFSSVGANG ESRELFISSG YGGMVRGWSA RPWPTFMNDA YYVVAQVGPY
MLQILRTLGS VFVQHKPFAV ARLYLDGSLV SAANTVVGDE LTAHADDVKG DAVRLTKVQP
DEKSQGLSGK FRDGNVGYVL EFAKKDSEHG WTFQISHKRA VWSEPTSAPG PDGTGKSGWI
EAISGGAKGE NYEGHGFGGQ LQIPVP
