Q5SIY4 (LEU3_THET8) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
3-isopropylmalate dehydrogenase
EC=1.1.1.85

Alternative name(s):
3-IPM-DH
Beta-IPM dehydrogenase
Short name=IMDH

Gene names

Name:	leuB
Ordered Locus Names:	TTHA1230

Organism

Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)

Taxonomic identifier

300852 [NCBI]

Taxonomic lineage

Bacteria › Deinococcus-Thermus › Deinococci › Thermales › Thermaceae › Thermus

Protein attributes

Sequence length	345 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the oxidation of 3-carboxy-2-hydroxy-4-methylpentanoate (3-isopropylmalate) to 3-carboxy-4-methyl-2-oxopentanoate. The product decarboxylates to 4-methyl-2 oxopentanoate. HAMAP MF_01033
Catalytic activity	(2R,3S)-3-isopropylmalate + NAD+ = 4-methyl-2-oxopentanoate + CO2 + NADH. HAMAP MF_01033
Cofactor	Binds 1 magnesium or manganese ion per subunit.
Pathway	Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine from 3-methyl-2-oxobutanoate: step 3/4. HAMAP MF_01033
Subunit structure	Homodimer. Ref.6 Ref.7 Ref.9
Subcellular location	Cytoplasm HAMAP MF_01033.
Sequence similarities	Belongs to the isocitrate and isopropylmalate dehydrogenases family. LeuB type 1 subfamily.
Biophysicochemical properties	Kinetic parameters: KM=1.26 µM for 3-isopropylmalate (at pH 8 and 60 degrees Celsius) Ref.4 KM=40.9 µM for NAD

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Branched-chain amino acid biosynthesis Leucine biosynthesis
Cellular component	Cytoplasm
Ligand	Magnesium Manganese Metal-binding NAD
Molecular function	Oxidoreductase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	leucine biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	3-isopropylmalate dehydrogenase activity Inferred from electronic annotation. Source: EC NAD binding Inferred from electronic annotation. Source: InterPro magnesium ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 345

345

3-isopropylmalate dehydrogenase HAMAP MF_01033

PRO_0000083775

Regions

Nucleotide binding

74 – 87

14

NAD HAMAP MF_01033

Nucleotide binding

274 – 286

13

NAD HAMAP MF_01033

Sites

Metal binding

217

1

Magnesium or manganese By similarity

Metal binding

241

1

Magnesium or manganese By similarity

Metal binding

245

1

Magnesium or manganese By similarity

Binding site

94

1

Substrate By similarity

Binding site

104

1

Substrate By similarity

Binding site

132

1

Substrate By similarity

Binding site

217

1

Substrate By similarity

Site

139

1

Important for catalysis

Site

185

1

Important for catalysis By similarity

Experimental info

Mutagenesis

139

1

Y → F: Large decrease in activity and a small decrease in substrate affinity. Ref.4

Sequence conflict

85

1

R → S in AAA16706. Ref.1

Secondary structure

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345

Helix Strand Turn

Details...

Beta strand

2 – 9

8

Helix

12 – 30

19

Beta strand

35 – 38

4

Helix

43 – 49

7

Beta strand

50 – 53

4

Helix

55 – 62

8

Beta strand

63 – 71

9

Turn

75 – 79

5

Helix

82 – 84

3

Helix

86 – 96

11

Beta strand

99 – 107

9

Helix

113 – 115

3

Beta strand

116 – 118

3

Helix

120 – 123

4

Beta strand

127 – 133

7

Turn

138 – 140

3

Beta strand

148 – 158

11

Helix

159 – 174

16

Turn

175 – 177

3

Beta strand

178 – 184

7

Turn

186 – 188

3

Helix

190 – 204

15

Beta strand

209 – 215

7

Helix

216 – 225

10

Helix

227 – 229

3

Beta strand

232 – 235

4

Helix

237 – 249

13

Helix

254 – 256

3

Beta strand

258 – 265

8

Beta strand

268 – 273

6

Helix

277 – 279

3

Turn

280 – 283

4

Helix

288 – 302

15

Helix

305 – 321

17

Helix

325 – 327

3

Helix

333 – 340

8

Sequences

	Sequence		Length	Mass (Da)
	Q5SIY4 [UniParc]. Last modified December 21, 2004. Version 1. Checksum: 3EFF8736312E2785	FASTA	345	36,780
	10 20 30 40 50 60 MKVAVLPGDG IGPEVTEAAL KVLRALDEAE GLGLAYEVFP FGGAAIDAFG EPFPEPTRKG 70 80 90 100 110 120 VEEAEAVLLG SVGGPKWDGL PRKIRPETGL LSLRKSQDLF ANLRPAKVFP GLERLSPLKE 130 140 150 160 170 180 EIARGVDVLI VRELTGGIYF GEPRGMSEAE AWNTERYSKP EVERVARVAF EAARKRRKHV 190 200 210 220 230 240 VSVDKANVLE VGEFWRKTVE EVGRGYPDVA LEHQYVDAMA MHLVRSPARF DVVVTGNIFG 250 260 270 280 290 300 DILSDLASVL PGSLGLLPSA SLGRGTPVFE PVHGSAPDIA GKGIANPTAA ILSAAMMLEH 310 320 330 340 AFGLVELARK VEDAVAKALL ETPPPDLGGS AGTEAFTATV LRHLA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"High guanine plus cytosine content in the third letter of codons of an extreme thermophile. DNA sequence of the isopropylmalate dehydrogenase of Thermus thermophilus." Kagawa Y., Nojima H., Nukiwa N., Ishizuka M., Nakajima T., Yasuhara T., Tanaka T., Oshima T. J. Biol. Chem. 259:2956-2960(1984) [PubMed: 6321488] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Hydrophobic interaction at the subunit interface contributes to the thermostability of 3-isopropylmalate dehydrogenase from an extreme thermophile, Thermus thermophilus." Kirino H., Aoki M., Aoshima M., Hayashi Y., Ohba M., Yamagishi A., Wakagi T., Oshima T. Eur. J. Biochem. 220:275-281(1994) [PubMed: 8119295] [Abstract] Cited for: SEQUENCE REVISION.
[3]	"Complete genome sequence of Thermus thermophilus HB8." Masui R., Kurokawa K., Nakagawa N., Tokunaga F., Koyama Y., Shibata T., Oshima T., Yokoyama S., Yasunaga T., Kuramitsu S. Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: HB8 / ATCC 27634 / DSM 579.
[4]	"Tyr-139 in Thermus thermophilus 3-isopropylmalate dehydrogenase is involved in catalytic function." Miyazaki K., Oshima T. FEBS Lett. 332:37-38(1993) [PubMed: 8405446] [Abstract] Cited for: ENZYME KINETICS, MUTAGENESIS OF TYR-139.
[5]	"Structure of 3-isopropylmalate dehydrogenase in complex with NAD+: ligand-induced loop closing and mechanism for cofactor specificity." Hurley J.H., Dean A.M. Structure 2:1007-1016(1994) [PubMed: 7881901] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH NAD.
[6]	"Cryocrystallography of 3-Isopropylmalate dehydrogenase from Thermus thermophilus and its chimeric enzyme." Nagata C., Moriyama H., Tanaka N., Nakasako M., Yamamoto M., Ueki T., Oshima T. Acta Crystallogr. D 52:623-630(1996) [PubMed: 15299625] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS), SUBUNIT.
[7]	"Three-dimensional structure of a highly thermostable enzyme, 3-isopropylmalate dehydrogenase of Thermus thermophilus at 2.2-A resolution." Imada K., Sato M., Tanaka N., Katsube Y., Matsuura Y., Oshima T. J. Mol. Biol. 222:725-738(1991) [PubMed: 1748999] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS), SUBUNIT.
[8]	"Crystal structures of 3-isopropylmalate dehydrogenase with mutations at the C-terminus: crystallographic analyses of structure-stability relationships." Nurachman Z., Akanuma S., Sato T., Oshima T., Tanaka N. Protein Eng. 13:253-258(2000) [PubMed: 10810156] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
[9]	"Design, X-ray crystallography, molecular modelling and thermal stability studies of mutant enzymes at site 172 of 3-isopropylmalate dehydrogenase from Thermus thermophilus." Qu C., Akanuma S., Tanaka N., Moriyama H., Oshima T. Acta Crystallogr. D 57:225-232(2001) [PubMed: 11173468] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS), SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

K01444 Genomic DNA. Translation: AAA16706.1.
AP008226 Genomic DNA. Translation: BAD71053.1.

PIR

DETWIT. S41223.

RefSeq

YP_144496.1. NC_006461.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1DPZ	X-ray	2.80	A/B	1-340	[»]
1DR0	X-ray	2.20	A/B	1-340	[»]
1DR8	X-ray	2.70	A/B	1-340	[»]
1G2U	X-ray	2.10	A	1-345	[»]
1GC8	X-ray	2.50	A/B	1-345	[»]
1GC9	X-ray	2.30	A	1-345	[»]
1HEX	X-ray	2.50	A	1-345	[»]
1IDM	X-ray	2.20	A	1-345	[»]
1IPD	X-ray	2.20	A	1-345	[»]
1OSI	X-ray	3.00	A/B/C/D	1-345	[»]
1OSJ	X-ray	2.35	A/B	1-345	[»]
1XAA	X-ray	2.10	A	1-345	[»]
1XAB	X-ray	2.10	A	1-345	[»]
1XAC	X-ray	2.10	A	1-345	[»]
1XAD	X-ray	2.10	A	1-345	[»]
2Y3Z	X-ray	1.83	A	1-345	[»]
2Y40	X-ray	2.50	A/B	1-345	[»]
2Y41	X-ray	2.20	A/B	1-345	[»]
2Y42	X-ray	2.50	A/B/C/D	1-345	[»]
2ZTW	X-ray	2.79	A	1-345	[»]

ProteinModelPortal

Q5SIY4.

SMR

Q5SIY4. Positions 1-345.

ModBase

Search...

Protein-protein interaction databases

STRING

Q5SIY4.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

3168996.

GenomeReviews

Gene locus TTHA1230 in contig AP008226_GR.

KEGG

ttj:TTHA1230.

NMPDR

fig|300852.3.peg.1459.

PATRIC

23957423. VBITheThe93045_1209.

Phylogenomic databases

eggNOG

COG0473.

HOGENOM

HBG518924.

OMA

AAMMLRF.

PhylomeDB

Q5SIY4.

ProtClustDB

PRK00772.

Enzyme and pathway databases

BioCyc

TTHE300852:TTHA1230-MONOMER.

Family and domain databases

HAMAP

MF_01033. LeuB_type1.
[Tree]

InterPro

IPR019818. IsoCit/isopropylmalate_DH_CS.
IPR001804. Isocitrate/isopropylmalate_DH.
IPR024084. IsoPropMal-DH-like_dom.
IPR004429. Isopropylmalate_DH.
[Graphical view]

Gene3D

G3DSA:3.40.718.10. IDH_IMDH. 1 hit.

KO

K00052.

PANTHER

PTHR11835. IDH_IMDH_dimeric. 1 hit.
PTHR11835:SF13. IPMDH. 1 hit.

Pfam

PF00180. Iso_dh. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00169. LeuB. 1 hit.

PROSITE

PS00470. IDH_IMDH. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

LEU3_THET8

Accession

Primary (citable) accession number: Q5SIY4

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 24, 2005
Last sequence update:	December 21, 2004
Last modified:	January 25, 2012
This is version 63 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program