ADH_CLOBE
ID ADH_CLOBE Reviewed; 351 AA.
AC P25984; Q9R559;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 04-DEC-2007, sequence version 2.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=NADP-dependent isopropanol dehydrogenase;
DE EC=1.1.1.80;
DE AltName: Full=CbADH;
GN Name=adh;
OS Clostridium beijerinckii (Clostridium MP).
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Clostridiaceae;
OC Clostridium.
OX NCBI_TaxID=1520;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=NRRL B-593;
RA Rifaat M.M., Chen J.S.;
RT "Cloning and sequence analysis of a gene encoding a medium-chain zinc-
RT containing alcohol dehydrogenase from the Gram-positive anaerobe
RT Clostridium beijerinckii NRRL B593.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PROTEIN SEQUENCE OF 1-21, CATALYTIC ACTIVITY, FUNCTION, SUBUNIT, COFACTOR,
RP AND BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=NESTE 255, and NRRL B-593;
RX PubMed=8349550; DOI=10.1128/jb.175.16.5097-5105.1993;
RA Ismaiel A.A., Zhu C.X., Colby G.D., Chen J.S.;
RT "Purification and characterization of a primary-secondary alcohol
RT dehydrogenase from two strains of Clostridium beijerinckii.";
RL J. Bacteriol. 175:5097-5105(1993).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) IN COMPLEX WITH NADP AND ZINC,
RP SUBUNIT, AND COFACTOR.
RX PubMed=9836873; DOI=10.1006/jmbi.1998.1750;
RA Korkhin Y., Kalb A.J., Peretz M., Bogin O., Burstein Y., Frolow F.;
RT "NADP-dependent bacterial alcohol dehydrogenases: crystal structure,
RT cofactor-binding and cofactor specificity of the ADHs of Clostridium
RT beijerinckii and Thermoanaerobacter brockii.";
RL J. Mol. Biol. 278:967-981(1998).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.97 ANGSTROMS) IN COMPLEX WITH ZINC.
RX PubMed=12381840; DOI=10.1110/ps.0222102;
RA Bogin O., Levin I., Hacham Y., Tel-Or S., Peretz M., Frolow F.,
RA Burstein Y.;
RT "Structural basis for the enhanced thermal stability of alcohol
RT dehydrogenase mutants from the mesophilic bacterium Clostridium
RT beijerinckii: contribution of salt bridging.";
RL Protein Sci. 11:2561-2574(2002).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH ZINC, SUBUNIT,
RP COFACTOR, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=20102159; DOI=10.1021/bi901730x;
RA Goihberg E., Peretz M., Tel-Or S., Dym O., Shimon L., Frolow F.,
RA Burstein Y.;
RT "Biochemical and structural properties of chimeras constructed by exchange
RT of cofactor-binding domains in alcohol dehydrogenases from thermophilic and
RT mesophilic microorganisms.";
RL Biochemistry 49:1943-1953(2010).
CC -!- FUNCTION: Alcohol dehydrogenase with a preference for medium chain
CC secondary alcohols, such as 2-butanol and isopropanol. Has very low
CC activity with primary alcohols, such as ethanol. Under physiological
CC conditions, the enzyme reduces aldehydes and 2-ketones to produce
CC secondary alcohols. Is active with acetaldehyde and propionaldehyde.
CC {ECO:0000269|PubMed:20102159, ECO:0000269|PubMed:8349550}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADP(+) + propan-2-ol = acetone + H(+) + NADPH;
CC Xref=Rhea:RHEA:21792, ChEBI:CHEBI:15347, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17824, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.80;
CC Evidence={ECO:0000269|PubMed:20102159, ECO:0000269|PubMed:8349550};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:20102159, ECO:0000269|PubMed:8349550,
CC ECO:0000269|PubMed:9836873};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:20102159,
CC ECO:0000269|PubMed:8349550, ECO:0000269|PubMed:9836873};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=5.7 mM for 2-butanol {ECO:0000269|PubMed:8349550};
CC KM=10 mM for isopropanol {ECO:0000269|PubMed:8349550};
CC KM=5.2 mM for 2-pentanol {ECO:0000269|PubMed:8349550};
CC KM=1 mM for acetone {ECO:0000269|PubMed:8349550};
CC KM=1.5 mM for 2-butanone {ECO:0000269|PubMed:8349550};
CC KM=0.03 mM for NADPH {ECO:0000269|PubMed:8349550};
CC pH dependence:
CC Optimum pH is 8. {ECO:0000269|PubMed:8349550};
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:12381840,
CC ECO:0000269|PubMed:20102159, ECO:0000269|PubMed:8349550,
CC ECO:0000269|PubMed:9836873}.
CC -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC family. {ECO:0000305}.
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DR EMBL; AF157307; AAA23199.2; -; Genomic_DNA.
DR PDB; 1JQB; X-ray; 1.97 A; A/B/C/D=1-351.
DR PDB; 1KEV; X-ray; 2.05 A; A/B/C/D=1-351.
DR PDB; 1PED; X-ray; 2.15 A; A/B/C/D=1-351.
DR PDB; 2B83; X-ray; 2.25 A; A/B/C/D=1-351.
DR PDB; 3FPL; X-ray; 1.90 A; A=1-152, A=296-351.
DR PDB; 3FSR; X-ray; 2.20 A; A/B/C/D=152-295.
DR PDB; 3FTN; X-ray; 2.19 A; A/B/C/D=152-295.
DR PDB; 6SCH; X-ray; 2.20 A; A/B/C/D=1-351.
DR PDBsum; 1JQB; -.
DR PDBsum; 1KEV; -.
DR PDBsum; 1PED; -.
DR PDBsum; 2B83; -.
DR PDBsum; 3FPL; -.
DR PDBsum; 3FSR; -.
DR PDBsum; 3FTN; -.
DR PDBsum; 6SCH; -.
DR AlphaFoldDB; P25984; -.
DR SMR; P25984; -.
DR EvolutionaryTrace; P25984; -.
DR GO; GO:0050009; F:isopropanol dehydrogenase (NADP+) activity; IEA:UniProtKB-EC.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR InterPro; IPR013149; ADH-like_C.
DR InterPro; IPR013154; ADH_N.
DR InterPro; IPR002328; ADH_Zn_CS.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020843; PKS_ER.
DR Pfam; PF08240; ADH_N; 1.
DR Pfam; PF00107; ADH_zinc_N; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00059; ADH_ZINC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Metal-binding; NADP;
KW Oxidoreductase; Zinc.
FT CHAIN 1..351
FT /note="NADP-dependent isopropanol dehydrogenase"
FT /id="PRO_0000160739"
FT BINDING 37
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:12381840,
FT ECO:0000269|PubMed:20102159, ECO:0000269|PubMed:9836873"
FT BINDING 59
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:12381840,
FT ECO:0000269|PubMed:20102159, ECO:0000269|PubMed:9836873"
FT BINDING 60
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:12381840,
FT ECO:0000269|PubMed:20102159, ECO:0000269|PubMed:9836873"
FT BINDING 150
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:12381840,
FT ECO:0000269|PubMed:20102159, ECO:0000269|PubMed:9836873"
FT BINDING 175..178
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:9836873"
FT BINDING 198..200
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:9836873"
FT BINDING 218
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:9836873"
FT BINDING 265..267
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:9836873"
FT BINDING 340
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:9836873"
FT STRAND 2..8
FT /evidence="ECO:0007829|PDB:3FPL"
FT STRAND 11..16
FT /evidence="ECO:0007829|PDB:3FPL"
FT STRAND 27..34
FT /evidence="ECO:0007829|PDB:3FPL"
FT HELIX 38..46
FT /evidence="ECO:0007829|PDB:3FPL"
FT STRAND 53..56
FT /evidence="ECO:0007829|PDB:3FPL"
FT STRAND 61..68
FT /evidence="ECO:0007829|PDB:3FPL"
FT STRAND 80..83
FT /evidence="ECO:0007829|PDB:3FPL"
FT STRAND 90..92
FT /evidence="ECO:0007829|PDB:3FPL"
FT HELIX 93..96
FT /evidence="ECO:0007829|PDB:3FPL"
FT HELIX 100..102
FT /evidence="ECO:0007829|PDB:3FPL"
FT TURN 106..109
FT /evidence="ECO:0007829|PDB:3FPL"
FT TURN 113..115
FT /evidence="ECO:0007829|PDB:3FPL"
FT STRAND 119..128
FT /evidence="ECO:0007829|PDB:3FPL"
FT HELIX 129..132
FT /evidence="ECO:0007829|PDB:3FPL"
FT HELIX 142..146
FT /evidence="ECO:0007829|PDB:3FPL"
FT TURN 147..150
FT /evidence="ECO:0007829|PDB:3FPL"
FT HELIX 151..161
FT /evidence="ECO:0007829|PDB:3FPL"
FT STRAND 170..173
FT /evidence="ECO:0007829|PDB:1JQB"
FT HELIX 177..187
FT /evidence="ECO:0007829|PDB:1JQB"
FT TURN 188..190
FT /evidence="ECO:0007829|PDB:1JQB"
FT STRAND 194..197
FT /evidence="ECO:0007829|PDB:1JQB"
FT HELIX 201..210
FT /evidence="ECO:0007829|PDB:1JQB"
FT STRAND 213..216
FT /evidence="ECO:0007829|PDB:1JQB"
FT HELIX 218..220
FT /evidence="ECO:0007829|PDB:1JQB"
FT HELIX 223..230
FT /evidence="ECO:0007829|PDB:1JQB"
FT TURN 231..233
FT /evidence="ECO:0007829|PDB:1JQB"
FT STRAND 236..241
FT /evidence="ECO:0007829|PDB:1JQB"
FT HELIX 248..255
FT /evidence="ECO:0007829|PDB:1JQB"
FT STRAND 256..264
FT /evidence="ECO:0007829|PDB:1JQB"
FT STRAND 270..277
FT /evidence="ECO:0007829|PDB:1JQB"
FT TURN 278..281
FT /evidence="ECO:0007829|PDB:1JQB"
FT HELIX 282..284
FT /evidence="ECO:0007829|PDB:1JQB"
FT STRAND 289..293
FT /evidence="ECO:0007829|PDB:1JQB"
FT HELIX 298..301
FT /evidence="ECO:0007829|PDB:3FTN"
FT HELIX 302..310
FT /evidence="ECO:0007829|PDB:3FPL"
FT HELIX 316..319
FT /evidence="ECO:0007829|PDB:3FPL"
FT STRAND 320..326
FT /evidence="ECO:0007829|PDB:3FPL"
FT HELIX 327..329
FT /evidence="ECO:0007829|PDB:3FPL"
FT HELIX 330..339
FT /evidence="ECO:0007829|PDB:3FPL"
FT STRAND 345..350
FT /evidence="ECO:0007829|PDB:3FPL"
SQ SEQUENCE 351 AA; 37716 MW; E1E925D37D7513B7 CRC64;
MKGFAMLGIN KLGWIEKERP VAGSYDAIVR PLAVSPCTSD IHTVFEGALG DRKNMILGHE
AVGEVVEVGS EVKDFKPGDR VIVPCTTPDW RSLEVQAGFQ QHSNGMLAGW KFSNFKDGVF
GEYFHVNDAD MNLAILPKDM PLENAVMITD MMTTGFHGAE LADIQMGSSV VVIGIGAVGL
MGIAGAKLRG AGRIIGVGSR PICVEAAKFY GATDILNYKN GHIVDQVMKL TNGKGVDRVI
MAGGGSETLS QAVSMVKPGG IISNINYHGS GDALLIPRVE WGCGMAHKTI KGGLCPGGRL
RAEMLRDMVV YNRVDLSKLV THVYHGFDHI EEALLLMKDK PKDLIKAVVI L
