HADB_CLODI
ID HADB_CLODI Reviewed; 408 AA.
AC Q5U924;
DT 16-MAR-2016, integrated into UniProtKB/Swiss-Prot.
DT 07-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 73.
DE RecName: Full=(R)-2-hydroxyisocaproyl-CoA dehydratase alpha subunit {ECO:0000303|PubMed:15654892};
DE EC=4.2.1.157 {ECO:0000269|PubMed:15654892};
GN Name=hadB {ECO:0000303|PubMed:15654892};
GN ORFNames=CD630DERM_03970, ERS445050_03310;
OS Clostridioides difficile (Peptoclostridium difficile).
OG Plasmid 2.
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Peptostreptococcaceae;
OC Clostridioides.
OX NCBI_TaxID=1496;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-11, FUNCTION,
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION,
RP COFACTOR, SUBUNIT, AND REACTION MECHANISM.
RX PubMed=15654892; DOI=10.1111/j.1742-4658.2004.04498.x;
RA Kim J., Darley D., Buckel W.;
RT "2-hydroxyisocaproyl-CoA dehydratase and its activator from Clostridium
RT difficile.";
RL FEBS J. 272:550-561(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=630Derm;
RA Magalhaes I.L.F., Oliveira U., Santos F.R., Vidigal T.H.D.A.,
RA Brescovit A.D., Santos A.J.;
RL Submitted (SEP-2014) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.82 ANGSTROMS) IN COMPLEX WITH IRON-SULFUR (4FE-4S)
RP AND SUBSTRATE ANALOG, FUNCTION, COFACTOR, SUBUNIT, AND REACTION MECHANISM.
RC PLASMID=2;
RX PubMed=21366233; DOI=10.1021/ja1076537;
RA Knauer S.H., Buckel W., Dobbek H.;
RT "Structural basis for reductive radical formation and electron recycling in
RT (R)-2-hydroxyisocaproyl-CoA dehydratase.";
RL J. Am. Chem. Soc. 133:4342-4347(2011).
CC -!- FUNCTION: Involved in the reductive branch of L-leucine fermentation.
CC Catalyzes the irreversible beta/alpha-elimination of water from (R)-2-
CC hydroxyisocaproyl-CoA to yield isocaprenoyl-CoA. This beta/alpha-
CC dehydration depends on the reductive formation of ketyl radicals on the
CC substrate generated by injection of a single electron from the ATP-
CC dependent activator protein HadI. The enzyme is specific for the R-
CC isomer. {ECO:0000269|PubMed:15654892, ECO:0000269|PubMed:21366233}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-2-hydroxy-4-methylpentanoyl-CoA = 4-methylpent-2-enoyl-CoA
CC + H2O; Xref=Rhea:RHEA:46924, ChEBI:CHEBI:15377, ChEBI:CHEBI:87119,
CC ChEBI:CHEBI:87120; EC=4.2.1.157;
CC Evidence={ECO:0000269|PubMed:15654892};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000269|PubMed:15654892, ECO:0000269|PubMed:21366233};
CC Note=Binds 1 [4Fe-4S] cluster. {ECO:0000269|PubMed:15654892,
CC ECO:0000269|PubMed:21366233};
CC -!- ACTIVITY REGULATION: Activated by HadI. {ECO:0000269|PubMed:15654892}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.05 mM for (R)-2-hydroxyisocaproyl-CoA
CC {ECO:0000269|PubMed:15654892};
CC -!- SUBUNIT: Part of the heterodimeric complex HadBC composed of (R)-2-
CC hydroxyisocaproyl-CoA dehydratase alpha (HadB) and beta (HadC) subunit.
CC {ECO:0000269|PubMed:15654892, ECO:0000269|PubMed:21366233}.
CC -!- SIMILARITY: Belongs to the FldB/FldC dehydratase alpha/beta subunit
CC family. {ECO:0000305}.
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DR EMBL; AY772816; AAV40819.1; -; Genomic_DNA.
DR EMBL; LN614756; CEJ96915.1; -; Genomic_DNA.
DR EMBL; LN831031; CKH72398.1; -; Genomic_DNA.
DR RefSeq; WP_009888224.1; NZ_WUUI01000021.1.
DR PDB; 3O3M; X-ray; 1.82 A; A/C=1-408.
DR PDB; 3O3N; X-ray; 2.30 A; A/C=1-408.
DR PDB; 3O3O; X-ray; 2.00 A; A=1-408.
DR PDBsum; 3O3M; -.
DR PDBsum; 3O3N; -.
DR PDBsum; 3O3O; -.
DR AlphaFoldDB; Q5U924; -.
DR SMR; Q5U924; -.
DR GeneID; 66352922; -.
DR KEGG; pdf:CD630DERM_03970; -.
DR BRENDA; 4.2.1.157; 1473.
DR SABIO-RK; Q5U924; -.
DR EvolutionaryTrace; Q5U924; -.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IDA:UniProtKB.
DR GO; GO:0016836; F:hydro-lyase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006551; P:leucine metabolic process; IDA:UniProtKB.
DR InterPro; IPR010327; FldB/FldC_alpha/beta.
DR Pfam; PF06050; HGD-D; 1.
PE 1: Evidence at protein level;
KW 3D-structure; 4Fe-4S; Direct protein sequencing; Iron; Iron-sulfur; Lyase;
KW Metal-binding; Plasmid.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:15654892"
FT CHAIN 2..408
FT /note="(R)-2-hydroxyisocaproyl-CoA dehydratase alpha
FT subunit"
FT /id="PRO_0000435662"
FT BINDING 55
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:21366233"
FT BINDING 84
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000269|PubMed:21366233"
FT BINDING 117
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000269|PubMed:21366233"
FT BINDING 346
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000269|PubMed:21366233"
FT HELIX 7..28
FT /evidence="ECO:0007829|PDB:3O3M"
FT STRAND 32..35
FT /evidence="ECO:0007829|PDB:3O3M"
FT HELIX 42..45
FT /evidence="ECO:0007829|PDB:3O3M"
FT TURN 46..48
FT /evidence="ECO:0007829|PDB:3O3M"
FT STRAND 50..52
FT /evidence="ECO:0007829|PDB:3O3M"
FT HELIX 54..63
FT /evidence="ECO:0007829|PDB:3O3M"
FT HELIX 67..76
FT /evidence="ECO:0007829|PDB:3O3M"
FT HELIX 85..96
FT /evidence="ECO:0007829|PDB:3O3M"
FT STRAND 100..102
FT /evidence="ECO:0007829|PDB:3O3M"
FT STRAND 108..113
FT /evidence="ECO:0007829|PDB:3O3M"
FT HELIX 119..131
FT /evidence="ECO:0007829|PDB:3O3M"
FT STRAND 135..138
FT /evidence="ECO:0007829|PDB:3O3M"
FT STRAND 145..147
FT /evidence="ECO:0007829|PDB:3O3M"
FT HELIX 150..171
FT /evidence="ECO:0007829|PDB:3O3M"
FT HELIX 177..197
FT /evidence="ECO:0007829|PDB:3O3M"
FT TURN 198..203
FT /evidence="ECO:0007829|PDB:3O3M"
FT HELIX 211..213
FT /evidence="ECO:0007829|PDB:3O3M"
FT HELIX 214..223
FT /evidence="ECO:0007829|PDB:3O3M"
FT HELIX 228..246
FT /evidence="ECO:0007829|PDB:3O3M"
FT STRAND 258..264
FT /evidence="ECO:0007829|PDB:3O3M"
FT HELIX 268..270
FT /evidence="ECO:0007829|PDB:3O3M"
FT HELIX 271..280
FT /evidence="ECO:0007829|PDB:3O3M"
FT STRAND 283..287
FT /evidence="ECO:0007829|PDB:3O3M"
FT HELIX 290..292
FT /evidence="ECO:0007829|PDB:3O3M"
FT TURN 293..295
FT /evidence="ECO:0007829|PDB:3O3M"
FT HELIX 303..311
FT /evidence="ECO:0007829|PDB:3O3M"
FT HELIX 314..316
FT /evidence="ECO:0007829|PDB:3O3M"
FT HELIX 319..332
FT /evidence="ECO:0007829|PDB:3O3M"
FT STRAND 336..345
FT /evidence="ECO:0007829|PDB:3O3M"
FT HELIX 347..350
FT /evidence="ECO:0007829|PDB:3O3M"
FT HELIX 353..364
FT /evidence="ECO:0007829|PDB:3O3M"
FT STRAND 368..373
FT /evidence="ECO:0007829|PDB:3O3M"
FT HELIX 378..380
FT /evidence="ECO:0007829|PDB:3O3M"
FT HELIX 383..401
FT /evidence="ECO:0007829|PDB:3O3M"
SQ SEQUENCE 408 AA; 46334 MW; 702A372CB6796AB5 CRC64;
MSEKKEARVV INDLLAEQYA NAFKAKEEGR PVGWSTSVFP QELAEVFDLN VLYPENQAAG
VAAKKGSLEL CEIAESKGYS IDLCAYARTN FGLLENGGCE ALDMPAPDFL LCCNNICNQV
IKWYENISRE LDIPLIMIDT TFNNEDEVTQ SRIDYIKAQF EEAIKQLEII SGKKFDPKKF
EEVMKISAEN GRLWKYSMSL PADSSPSPMN GFDLFTYMAV IVCARGKKET TEAFKLLIEE
LEDNMKTGKS SFRGEEKYRI MMEGIPCWPY IGYKMKTLAK FGVNMTGSVY PHAWALQYEV
NDLDGMAVAY STMFNNVNLD RMTKYRVDSL VEGKCDGAFY HMNRSCKLMS LIQYEMQRRA
AEETGLPYAG FDGDQADPRA FTNAQFETRI QGLVEVMEER KKLNRGEI
