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UniProtKB - Q8F3Q1 (CIMA_LEPIN)
Protein
(R)-citramalate synthase CimA
Gene
cimA
Organism
Leptospira interrogans serogroup Icterohaemorrhagiae serovar Lai (strain 56601)
Status
Functioni
Catalyzes the condensation of pyruvate and acetyl-coenzyme A to form (R)-citramalate (PubMed:15292141, PubMed:18498255, PubMed:19351325).
Shows strict substrate specificity for pyruvate. Cannot use alpha-ketoisovalerate, alpha-ketobutyrate, alpha-ketoisocaproate, alpha-ketoglutarate or glyoxylate (PubMed:15292141, PubMed:18498255).
3 PublicationsCatalytic activityi
Cofactori
Mn2+1 PublicationNote: Mn2+ is the most effective activator, followed by Co2+, Ca2+, Mg2+ and Ni2+.1 Publication
Activity regulationi
Regulated by the end-product isoleucine via a feedback inhibition. The binding of isoleucine has inhibitory effects on the binding of both pyruvate and acetyl-CoA. May act via conformational change of the dimer interface of the regulatory domain, leading to inhibition of the catalytic reaction.1 Publication
Kineticsi
kcat is 2.41 sec(-1) (PubMed:15292141). kcat is 10.3 sec(-1) with acetyl-CoA as substrate (PubMed:18498255). kcat is 9.13 sec(-1) with pyruvate as substrate (PubMed:18498255).2 Publications
- KM=43 µM for pyruvate1 Publication
- KM=60 µM for pyruvate1 Publication
- KM=1118 µM for acetyl-CoA1 Publication
Temperature dependencei
Optimum temperature is 35-40 degrees Celsius.1 Publication
: L-isoleucine biosynthesis Pathwayi
This protein is involved in step 1 of the subpathway that synthesizes 2-oxobutanoate from pyruvate.1 Publication This subpathway is part of the pathway L-isoleucine biosynthesis, which is itself part of Amino-acid biosynthesis.View all proteins of this organism that are known to be involved in the subpathway that synthesizes 2-oxobutanoate from pyruvate, the pathway L-isoleucine biosynthesis and in Amino-acid biosynthesis.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 16 | Proton donor1 Publication | 1 | |
Metal bindingi | 17 | Manganese2 Publications | 1 | |
Binding sitei | 144 | Pyruvate1 Publication | 1 | |
Active sitei | 146 | Proton acceptor1 Publication | 1 | |
Binding sitei | 179 | Pyruvate1 Publication | 1 | |
Metal bindingi | 207 | Manganese; via tele nitrogen2 Publications | 1 | |
Metal bindingi | 209 | Manganese; via tele nitrogen2 Publications | 1 |
GO - Molecular functioni
- (R)-citramalate synthase activity Source: UniProtKB-EC
- 2-isopropylmalate synthase activity Source: GO_Central
- lyase activity Source: UniProtKB-KW
- metal ion binding Source: UniProtKB-KW
GO - Biological processi
- isoleucine biosynthetic process Source: UniProtKB-UniPathway
- leucine biosynthetic process Source: GO_Central
Keywordsi
Molecular function | Lyase, Transferase |
Biological process | Amino-acid biosynthesis, Branched-chain amino acid biosynthesis, Isoleucine biosynthesis |
Ligand | Manganese, Metal-binding, Pyruvate |
Enzyme and pathway databases
UniPathwayi | UPA00047;UER00066 |
Names & Taxonomyi
Protein namesi | Recommended name: (R)-citramalate synthase CimACurated (EC:2.3.1.1823 Publications)Alternative name(s): LiCMS1 Publication |
Gene namesi | Name:cimA1 Publication Ordered Locus Names:LA_2350Imported |
Organismi | Leptospira interrogans serogroup Icterohaemorrhagiae serovar Lai (strain 56601) |
Taxonomic identifieri | 189518 [NCBI] |
Taxonomic lineagei | Bacteria › Spirochaetes › Leptospirales › Leptospiraceae › Leptospira › |
Proteomesi |
|
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 16 | R → K or Q: Loss of activity. 1 Publication | 1 | |
Mutagenesisi | 17 | D → A: 34-fold increase in Km for pyruvate and 315-fold decrease in kcat. 1 Publication | 1 | |
Mutagenesisi | 17 | D → N: 4.4-fold increase in Km for pyruvate and 480-fold decrease in kcat. 1 Publication | 1 | |
Mutagenesisi | 81 | L → A: 4.7-fold increase in Km for pyruvate and 15.7-fold decrease in kcat. 1 Publication | 1 | |
Mutagenesisi | 81 | L → V: 3.3-fold increase in Km for pyruvate and 10.1-fold decrease in kcat. 1 Publication | 1 | |
Mutagenesisi | 83 | F → A: 5-fold increase in Km for acetyl-CoA and 120-fold decrease in kcat. 1 Publication | 1 | |
Mutagenesisi | 104 | L → V: 1.8-fold increase in Km for pyruvate and 3.4-fold decrease in kcat. 1 Publication | 1 | |
Mutagenesisi | 144 | Y → L: 259-fold increase in Km for pyruvate and 76-fold decrease in kcat. 1 Publication | 1 | |
Mutagenesisi | 144 | Y → V: 114-fold increase in Km for pyruvate and 5.3-fold decrease in kcat. 1 Publication | 1 | |
Mutagenesisi | 146 | E → D or Q: Minor effects on the binding of acetyl-CoA, but causes a strong decrease in kcat. 1 Publication | 1 | |
Mutagenesisi | 179 | T → A: 16.4-fold increase in Km for pyruvate and 186-fold decrease in kcat. 1 Publication | 1 | |
Mutagenesisi | 302 | H → A or N: Loss of activity. 1 Publication | 1 | |
Mutagenesisi | 304 | D → A: 5.2-fold increase in Km for acetyl-CoA and 16.6-fold decrease in kcat. 1 Publication | 1 | |
Mutagenesisi | 310 | N → A: 2.2-fold increase in Km for acetyl-CoA and 1.7-fold decrease in kcat. 1 Publication | 1 | |
Mutagenesisi | 311 | L → A: 8-fold increase in Km for acetyl-CoA and 6-fold decrease in kcat. 1 Publication | 1 | |
Mutagenesisi | 312 | Y → A: Loss of activity. 1 Publication | 1 | |
Mutagenesisi | 430 | Y → L: No change in Km for acetyl-CoA and 2.3-fold decrease in kcat. Severely impairs inhibition by isoleucine. 1 Publication | 1 | |
Mutagenesisi | 431 | D → A: 1.8-fold decrease in Km for acetyl-CoA and 5-fold decrease in kcat. 1 Publication | 1 | |
Mutagenesisi | 451 | L → V: 1.5-fold increase in Km for acetyl-CoA and 4.3 decrease in kcat. 1 Publication | 1 | |
Mutagenesisi | 454 | Y → A: 1.4 decrease in Km for acetyl-CoA and 17-fold decrease in kcat. Still inhibited by isoleucine and weakly inhibited by leucine. 1 Publication | 1 | |
Mutagenesisi | 458 | I → A: 1.3-fold decrease in Km for acetyl-CoA and 14-fold decrease in kcat. Abolishes inhibition by isoleucine. 1 Publication | 1 | |
Mutagenesisi | 464 | T → A: 1.8-fold decrease in Km for acetyl-CoA and 4.3-fold decrease in kcat. 1 Publication | 1 | |
Mutagenesisi | 468 | V → A: No change in Km for acetyl-CoA and 2-fold decrease in kcat. Increases inhibition by isoleucine and leucine becomes an effective inhibitor. 1 Publication | 1 | |
Mutagenesisi | 493 | P → A: 1.5-fold decrease in Km for acetyl-CoA and 2.6-fold decrease in kcat. 1 Publication | 1 | |
Mutagenesisi | 495 | Q → A: 1.6-fold decrease in Km for acetyl-CoA and 2.8-fold decrease in kcat. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000449424 | 1 – 516 | (R)-citramalate synthase CimAAdd BLAST | 516 |
Expressioni
Inductioni
Expression is repressed by isoleucine but not by leucine.1 Publication
Interactioni
Subunit structurei
Homodimer.
2 PublicationsProtein-protein interaction databases
STRINGi | 189518.LA_2350 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q8F3Q1 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q8F3Q1 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 8 – 269 | Pyruvate carboxyltransferasePROSITE-ProRule annotationAdd BLAST | 262 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 16 – 17 | Pyruvate binding1 Publication | 2 |
Domaini
Contains a catalytic N-terminal domain and a C-terminal regulatory domain, linked together by a flexible region (PubMed:18498255, PubMed:19351325). The catalytic domain consists of a TIM barrel flanked by an extended C-terminal region. The active site is located at the center of the TIM barrel near the C-terminal ends of the beta-strands and is composed of conserved residues of the beta-strands of one subunit and the C-terminal region of the other (PubMed:18498255).2 Publications
Sequence similaritiesi
Belongs to the alpha-IPM synthase/homocitrate synthase family.Curated
Phylogenomic databases
HOGENOMi | CLU_022158_0_1_12 |
OMAi | DWSNGMR |
Family and domain databases
Gene3Di | 3.20.20.70, 1 hit |
InterProi | View protein in InterPro IPR013709, 2-isopropylmalate_synth_dimer IPR002034, AIPM/Hcit_synth_CS IPR013785, Aldolase_TIM IPR036230, LeuA_allosteric_dom_sf IPR000891, PYR_CT |
Pfami | View protein in Pfam PF00682, HMGL-like, 1 hit PF08502, LeuA_dimer, 1 hit |
SMARTi | View protein in SMART SM00917, LeuA_dimer, 1 hit |
SUPFAMi | SSF110921, SSF110921, 1 hit |
PROSITEi | View protein in PROSITE PS00815, AIPM_HOMOCIT_SYNTH_1, 1 hit PS50991, PYR_CT, 1 hit |
i Sequence
Sequence statusi: Complete.
Q8F3Q1-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MTKVETRLEI LDVTLRDGEQ TRGVSFSTSE KLNIAKFLLQ KLNVDRVEIA
60 70 80 90 100
SARVSKGELE TVQKIMEWAA TEQLTERIEI LGFVDGNKTV DWIKDSGAKV
110 120 130 140 150
LNLLTKGSLH HLEKQLGKTP KEFFTDVSFV IEYAIKSGLK INVYLEDWSN
160 170 180 190 200
GFRNSPDYVK SLVEHLSKEH IERIFLPDTL GVLSPEETFQ GVDSLIQKYP
210 220 230 240 250
DIHFEFHGHN DYDLSVANSL QAIRAGVKGL HASINGLGER AGNTPLEALV
260 270 280 290 300
TTIHDKSNSK TNINEIAITE ASRLVEVFSG KRISANRPIV GEDVFTQTAG
310 320 330 340 350
VHADGDKKGN LYANPILPER FGRKRSYALG KLAGKASISE NVKQLGMVLS
360 370 380 390 400
EVVLQKVLER VIELGDQNKL VTPEDLPFII ADVSGRTGEK VLTIKSCNIH
410 420 430 440 450
SGIGIRPHAQ IELEYQGKIH KEISEGDGGY DAFMNALTKI TNRLGISIPK
460 470 480 490 500
LIDYEVRIPP GGKTDALVET RITWNKSLDL EEDQTFKTMG VHPDQTVAAV
510
HATEKMLNQI LQPWQI
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AE010300 Genomic DNA Translation: AAN49549.1 |
RefSeqi | NP_712531.1, NC_004342.2 WP_000169689.1, NC_004342.2 |
Genome annotation databases
EnsemblBacteriai | AAN49549; AAN49549; LA_2350 |
KEGGi | lil:LA_2350 |
PATRICi | fig|189518.3.peg.2333 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AE010300 Genomic DNA Translation: AAN49549.1 |
RefSeqi | NP_712531.1, NC_004342.2 WP_000169689.1, NC_004342.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3BLE | X-ray | 2.00 | A | 1-325 | [»] | |
3BLF | X-ray | 2.60 | A | 1-325 | [»] | |
3BLI | X-ray | 2.50 | A | 1-325 | [»] | |
3F6G | X-ray | 2.00 | A/B | 390-516 | [»] | |
3F6H | X-ray | 2.70 | A/B | 390-516 | [»] | |
SMRi | Q8F3Q1 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
STRINGi | 189518.LA_2350 |
Genome annotation databases
EnsemblBacteriai | AAN49549; AAN49549; LA_2350 |
KEGGi | lil:LA_2350 |
PATRICi | fig|189518.3.peg.2333 |
Phylogenomic databases
HOGENOMi | CLU_022158_0_1_12 |
OMAi | DWSNGMR |
Enzyme and pathway databases
UniPathwayi | UPA00047;UER00066 |
Miscellaneous databases
EvolutionaryTracei | Q8F3Q1 |
Family and domain databases
Gene3Di | 3.20.20.70, 1 hit |
InterProi | View protein in InterPro IPR013709, 2-isopropylmalate_synth_dimer IPR002034, AIPM/Hcit_synth_CS IPR013785, Aldolase_TIM IPR036230, LeuA_allosteric_dom_sf IPR000891, PYR_CT |
Pfami | View protein in Pfam PF00682, HMGL-like, 1 hit PF08502, LeuA_dimer, 1 hit |
SMARTi | View protein in SMART SM00917, LeuA_dimer, 1 hit |
SUPFAMi | SSF110921, SSF110921, 1 hit |
PROSITEi | View protein in PROSITE PS00815, AIPM_HOMOCIT_SYNTH_1, 1 hit PS50991, PYR_CT, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CIMA_LEPIN | |
Accessioni | Q8F3Q1Primary (citable) accession number: Q8F3Q1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 22, 2020 |
Last sequence update: | March 1, 2003 | |
Last modified: | February 23, 2022 | |
This is version 129 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Prokaryotic Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families