ID ADH_THEBR Reviewed; 352 AA. AC P14941; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1990, sequence version 1. DT 02-SEP-2026, entry version 156. DE RecName: Full=NADP-dependent isopropanol dehydrogenase; DE EC=1.1.1.80; GN Name=adh; OS Thermoanaerobacter brockii (Thermoanaerobium brockii). OC Bacteria; Bacillati; Bacillota; Clostridia; Thermoanaerobacterales; OC Thermoanaerobacteraceae; Thermoanaerobacter. OX NCBI_TaxID=29323; RN [1] RP PROTEIN SEQUENCE. RC STRAIN=ATCC 53556 / DSM 1457 / HTD4; RX PubMed=2790012; DOI=10.1021/bi00442a004; RA Peretz M., Burstein Y.; RT "Amino acid sequence of alcohol dehydrogenase from the thermophilic RT bacterium Thermoanaerobium brockii."; RL Biochemistry 28:6549-6555(1989). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 53556 / DSM 1457 / HTD4; RA Burstein Y.; RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases. RN [3] RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) IN COMPLEX WITH NADP AND ZINC. 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 (1.90 ANGSTROMS) OF 153-295 IN COMPLEX WITH ZINC, RP FUNCTION, SUBUNIT, COFACTOR, 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 also active with acetaldehyde and CC propionaldehyde. {ECO:0000269|PubMed:20102159}. CC -!- CATALYTIC ACTIVITY: CC Reaction=propan-2-ol + NADP(+) = acetone + NADPH + H(+); 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}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:20102159}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:20102159}; CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:20102159, CC ECO:0000269|PubMed:9836873}. CC -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase CC family. {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; X64841; CAA46053.1; -; Genomic_DNA. DR PIR; A32973; A32973. DR PDB; 1BXZ; X-ray; 2.99 A; A/B/C/D=1-352. DR PDB; 1YKF; X-ray; 2.50 A; A/B/C/D=1-352. DR PDB; 2NVB; X-ray; 2.80 A; A/B/C/D=1-352. DR PDB; 3FPC; X-ray; 1.40 A; A/B/C/D=4-162, A/B/C/D=295-352. DR PDB; 3FPL; X-ray; 1.90 A; A=1-7, A=165-301. DR PDB; 3FSR; X-ray; 2.20 A; A/B/C/D=1-164, A/B/C/D=302-352. DR PDB; 3FTN; X-ray; 2.19 A; A/B/C/D=8-165, A/B/C/D=302-352. DR PDB; 6SDM; X-ray; 2.85 A; A/B/C/D=1-352. DR PDB; 7F3P; X-ray; 2.60 A; A/B/C/D=1-352. DR PDB; 7UTC; X-ray; 1.85 A; A/B/C/D=1-352. DR PDB; 7UUT; X-ray; 1.89 A; A/B/C/D=1-352. DR PDB; 7UX4; X-ray; 2.23 A; A/B/C/D=1-352. DR PDB; 7XL5; X-ray; 2.60 A; A/B/C/D=2-352. DR PDB; 7XY9; EM; 2.12 A; A/B/C/D=2-352. DR AlphaFoldDB; P14941; -. DR EMDB; EMD-33514; -. DR SMR; P14941; -. DR DrugBank; DB02606; 2-Butanol. DR DrugBank; DB03461; Nicotinamide adenine dinucleotide phosphate. DR BRENDA; 1.1.1.2; 1463. DR BRENDA; 1.1.1.80; 1463. DR EvolutionaryTrace; P14941; -. DR GO; GO:0050009; F:isopropanol dehydrogenase (NADP+) activity; IEA:UniProtKB-EC. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR CDD; cd08285; NADP_ADH; 1. DR Gene3D; 3.90.180.10; Medium-chain alcohol dehydrogenases, catalytic domain; 1. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. DR InterPro; IPR013149; ADH-like_C. DR InterPro; IPR013154; ADH-like_N. DR InterPro; IPR002328; ADH_Zn_CS. DR InterPro; IPR020843; ER. DR InterPro; IPR011032; GroES-like_sf. DR InterPro; IPR036291; NAD(P)-bd_dom_sf. DR PANTHER; PTHR42813:SF4; NADP-DEPENDENT ISOPROPANOL DEHYDROGENASE; 1. DR PANTHER; PTHR42813; ZINC-TYPE ALCOHOL DEHYDROGENASE-LIKE; 1. DR Pfam; PF08240; ADH_N; 1. DR Pfam; PF00107; ADH_zinc_N; 1. DR SMART; SM00829; PKS_ER; 1. DR SUPFAM; SSF50129; GroES-like; 1. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. DR PROSITE; PS00059; ADH_ZINC; 1. DR PDBsum; 1BXZ; -. DR PDBsum; 1YKF; -. DR PDBsum; 2NVB; -. DR PDBsum; 3FPC; -. DR PDBsum; 3FPL; -. DR PDBsum; 3FSR; -. DR PDBsum; 3FTN; -. DR PDBsum; 6SDM; -. DR PDBsum; 7F3P; -. DR PDBsum; 7UTC; -. DR PDBsum; 7UUT; -. DR PDBsum; 7UX4; -. DR PDBsum; 7XL5; -. DR PDBsum; 7XY9; -. PE 1: Evidence at protein level; KW 3D-structure; Direct protein sequencing; Metal-binding; NADP; KW Oxidoreductase; Zinc. FT CHAIN 1..352 FT /note="NADP-dependent isopropanol dehydrogenase" FT /id="PRO_0000160749" FT BINDING 37 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:20102159, FT 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:20102159, FT 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:20102159, FT 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:3FPC" FT STRAND 11..16 FT /evidence="ECO:0007829|PDB:3FPC" FT HELIX 18..20 FT /evidence="ECO:0007829|PDB:3FPC" FT STRAND 27..35 FT /evidence="ECO:0007829|PDB:3FPC" FT HELIX 38..45 FT /evidence="ECO:0007829|PDB:3FPC" FT STRAND 53..56 FT /evidence="ECO:0007829|PDB:3FPC" FT STRAND 60..68 FT /evidence="ECO:0007829|PDB:3FPC" FT STRAND 80..83 FT /evidence="ECO:0007829|PDB:3FPC" FT STRAND 90..92 FT /evidence="ECO:0007829|PDB:3FPC" FT HELIX 93..96 FT /evidence="ECO:0007829|PDB:3FPC" FT HELIX 100..102 FT /evidence="ECO:0007829|PDB:3FPC" FT TURN 106..109 FT /evidence="ECO:0007829|PDB:3FPC" FT TURN 113..115 FT /evidence="ECO:0007829|PDB:3FPC" FT STRAND 119..122 FT /evidence="ECO:0007829|PDB:3FPC" FT STRAND 124..128 FT /evidence="ECO:0007829|PDB:3FPC" FT HELIX 129..132 FT /evidence="ECO:0007829|PDB:3FPC" FT STRAND 133..135 FT /evidence="ECO:0007829|PDB:7F3P" FT HELIX 142..145 FT /evidence="ECO:0007829|PDB:3FPC" FT HELIX 148..152 FT /evidence="ECO:0007829|PDB:3FPC" FT HELIX 153..161 FT /evidence="ECO:0007829|PDB:3FPC" FT STRAND 170..173 FT /evidence="ECO:0007829|PDB:7UTC" FT HELIX 177..188 FT /evidence="ECO:0007829|PDB:7UTC" FT STRAND 194..197 FT /evidence="ECO:0007829|PDB:7UTC" FT HELIX 201..209 FT /evidence="ECO:0007829|PDB:7UTC" FT STRAND 213..216 FT /evidence="ECO:0007829|PDB:7UTC" FT HELIX 218..220 FT /evidence="ECO:0007829|PDB:7UTC" FT HELIX 223..230 FT /evidence="ECO:0007829|PDB:7UTC" FT TURN 231..233 FT /evidence="ECO:0007829|PDB:7UTC" FT STRAND 236..241 FT /evidence="ECO:0007829|PDB:7UTC" FT HELIX 248..255 FT /evidence="ECO:0007829|PDB:7UTC" FT STRAND 256..264 FT /evidence="ECO:0007829|PDB:7UTC" FT HELIX 266..268 FT /evidence="ECO:0007829|PDB:7XL5" FT STRAND 272..277 FT /evidence="ECO:0007829|PDB:7UTC" FT TURN 278..281 FT /evidence="ECO:0007829|PDB:7UTC" FT HELIX 282..284 FT /evidence="ECO:0007829|PDB:7UTC" FT STRAND 289..293 FT /evidence="ECO:0007829|PDB:7UTC" FT HELIX 294..296 FT /evidence="ECO:0007829|PDB:7UTC" FT HELIX 298..310 FT /evidence="ECO:0007829|PDB:3FPC" FT HELIX 316..319 FT /evidence="ECO:0007829|PDB:3FPC" FT STRAND 320..326 FT /evidence="ECO:0007829|PDB:3FPC" FT HELIX 329..338 FT /evidence="ECO:0007829|PDB:3FPC" FT STRAND 345..350 FT /evidence="ECO:0007829|PDB:3FPC" SQ SEQUENCE 352 AA; 37647 MW; E124A5351AD55185 CRC64; MKGFAMLSIG KVGWIEKEKP APGPFDAIVR PLAVAPCTSD IHTVFEGAIG ERHNMILGHE AVGEVVEVGS EVKDFKPGDR VVVPAITPDW RTSEVQRGYH QHSGGMLAGW KFSNVKDGVF GEFFHVNDAD MNLAHLPKEI PLEAAVMIPD MMTTGFHGAE LADIELGATV AVLGIGPVGL MAVAGAKLRG AGRIIAVGSR PVCVDAAKYY GATDIVNYKD GPIESQIMNL TEGKGVDAAI IAGGNADIMA TAVKIVKPGG TIANVNYFGE GEVLPVPRLE WGCGMAHKTI KGGLCPGGRL RMERLIDLVF YKRVDPSKLV THVFRGFDNI EKAFMLMKDK PKDLIKPVVI LA //