4CTS,1A59,1AJ8,1AMZ,1CSH,1IXE,1NXG,2C6X,2CTS,2H12,2IFC,6CSC,6CTS


Conserved Protein Domain Family
citrate_synt

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cd06101: citrate_synt 
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Citrate synthase (CS) catalyzes the condensation of acetyl coenzyme A (AcCoA) and oxalacetate (OAA) to form citrate and coenzyme A (CoA), the first step in the oxidative citric acid cycle (TCA or Krebs cycle). Peroxisomal CS is involved in the glyoxylate cycle. This group also includes CS proteins which functions as a 2-methylcitrate synthase (2MCS). 2MCS catalyzes the condensation of propionyl-CoA (PrCoA) and OAA to form 2-methylcitrate and CoA during propionate metabolism. This group contains proteins which functions exclusively as either a CS or a 2MCS, as well as those with relaxed specificity which have dual functions as both a CS and a 2MCS. The overall CS reaction is thought to proceed through three partial reactions and involves both closed and open conformational forms of the enzyme: a) the carbanion or equivalent is generated from AcCoA by base abstraction of a proton, b) the nucleophilic attack of this carbanion on OAA to generate citryl-CoA, and c) the hydrolysis of citryl-CoA to produce citrate and CoA. There are two types of CSs: type I CS and type II CSs. Type I CSs are found in eukarya, gram-positive bacteria, archaea, and in some gram-negative bacteria and form homodimers with both subunits participating in the active site. Type II CSs are unique to gram-negative bacteria and are homohexamers of identical subunits (approximated as a trimer of dimers). Some type II CSs are strongly and specifically inhibited by NADH through an allosteric mechanism. This subgroup includes both gram-positive and gram-negative bacteria.
Statistics
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PSSM-Id: 99855
View PSSM: cd06101
Aligned: 21 rows
Threshold Bit Score: 263.79
Threshold Setting Gi: 13473292
Created: 6-Mar-2002
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
  next features
Conserved site includes 26 residues -Click on image for an interactive view with Cn3D
Feature 1:active site [active site]
Evidence:
  • Comment:The overall CS reaction involves both closed and open conformational forms of the enzyme.
  • Structure:6CSC_A, Gallus gallus type I CS dimer bound with citrate, contacts at 3.5 A.
    View structure with Cn3D
  • Structure:6CTS_A, Gallus gallus heart type I CS monomer bound with citryl-thioester CoA, contacts at 3.5 A.
    View structure with Cn3D
  • Comment:Citryl-thioester CoA is a potent inhibitor of chicken heart CS. It is extremely similar to the citryl-CoA intermediate; the only difference is that the O-3 of citrate has been substituted with two hydrogen atoms preventing hydrolysis of the compound.
  • Citation:PMID 7120407
  • Structure:4CTS_A, Sus scrofa type I CS dimer bound with OAA, contacts at 3.5 A.
    View structure with Cn3D
  • Citation:PMID 6716477
  • Structure:2H12_A, Acetobacter aceti type II CS homo-hexamer bound with oxaloacetate, contacts at 3.5 A.
    View structure with Cn3D
  • Structure:1AJ8_A, Pyrococcus furiosus CS dimer bound with coenzyme A, contacts at 3.5 A.
    View structure with Cn3D
  • Citation:PMID 9254593
  • Structure:2C6X_A, Bacillus subtilis CS-I dimer bound with citrate, contacts at 3.5A
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1        #                                                                            
4CTS_A     43 GGMRGMK-----GLVYETsVLDPde----------gIRFRGYSIPECqkmlpkakggeeplPEGLFWLLVTGQIPteeqv 107 pig
1AMZ_A     41 GGMRGMK-----GLIYETsVLDPde----------gIRFRGFSIPECqkllpkagggeeplPEGLFWLLVTGQIPtpeqv 105 chicken
1CSH_A     41 GGMRGMK-----GLIYETsVLDPde----------gIRFRGFSIPECqkllpkagggeeplPEGLFWLLVTGQIPtpeqv 105 chicken
2C6X_A      3 YGLKGIT-----CVETSIsHIDGek---------grLIYRGHHAKDIaln---------hsFEEAAYLILFGKLPsteel 59  Bacillus subtilis
2CTS_A     43 GGMRGMK-----GLVYETsVLDPde----------gIRFRGYSIPECqkmlpkakggeeplPEGLFWLLVTGQIPteeqv 107 pig
2IFC_A      9 KGLEDVN-----IKWTRLtTIDGnk---------giLRYGGYSVEDIias--------gaqDEEIQYLFLYGNLPteqel 66  Thermoplasma acido...
6CSC_A     43 GGMRGMK-----GLIYETsVLDPde----------gIRFRGFSIPECqkllpkagggeeplPEGLFWLLVTGQIPtpeqv 107 chicken
6CTS_A     43 GGMRGMK-----GLVYETsVLDPde----------gIRFRGFSIPECqkllpkggxggeplPEGLFWLLVTGQIPtgaqv 107 chicken
AAF09126   28 KGLRDINgkgvlAGLTNIsAIHSfdkegn--qipgvLEYRAYNIKDIvsdlrs---knrfgFEEMTYLLLFGELPsakel 102 Lactococcus lactis...
NP_104859  58 RGRSPSA-----IAESAIaWGEPsiataistvwhghLIYRGRDAAVLsdn---------atLEETAAVLWGLPEPirfea 123 Mesorhizobium loti...
Feature 1                                                                                     
4CTS_A    108 swlskewakraalpshvvtmldnfptnlhpmsqlsaaitalnsesnfarayaegihrtkyweliyedcmdliaklpcvaa 187 pig
1AMZ_A    106 swvskewakraalpshvvtmldnfptnlhpmsqlsaaitalnsesnfarayaeginrtkywefvyedamdliaklpcvaa 185 chicken
1CSH_A    106 swvskewakraalpshvvtmldnfptnlhpmsqlsaaitalnsesnfarayaeginrtkywefvyedamdliaklpcvaa 185 chicken
2C6X_A     60 qvfkdklaaernlpehierliqslpnnmddmsvlrtvvsa---------------lgentytfhpkteeairliaitpsi 124 Bacillus subtilis
2CTS_A    108 swlskewakraalpshvvtmldnfptnlhpmsqlsaaitalnsesnfarayaegihrtkyweliyedcmdliaklpcvaa 187 pig
2IFC_A     67 rkyketvqkgykipdfvinairqlpresdavamqmaavaama-----------asetkfkwnkdtdrdvaaemigrmsai 135 Thermoplasma acido...
6CSC_A    108 swvskewakraalpshvvtmldnfptnlhpmsqlsaaitalnsesnfarayaeginrtkywefvyedamdliaklpcvaa 187 chicken
6CTS_A    108 swlskewakraalpshvvtmldnfptnlhpmsqlsaaitalnsesnfarayaegilrtkywemvyesamdliaklpcvaa 187 chicken
AAF09126  103 qefqillaskrtlpeffvretiltnpssdvmnsmsrcllalasydk----kasdisienvleqslaliadfpllaiysyq 178 Lactococcus lactis...
NP_104859 124 papdaprqpgrasafaqlallagqar-------------------------------------------pslgrsaaslc 160 Mesorhizobium loti...
Feature 1                                                          #   #                      
4CTS_A    188 kiyrnlyregssigaidsklDWSHNFTNMlgy---tdaQFTELMRLYLTIHSDHEggNVSAHTSHLVGSALSDPYLSFAA 264 pig
1AMZ_A    186 kiyrnlyragssigaidsklDWSHNFTNMlgy---tdpQFTELMRLYLTIHSDHEggNVSAHTSHLVGSALSDPYLSFAA 262 chicken
1CSH_A    186 kiyrnlyragssigaidsklDWSHNFTNMlgy---tdpQFTELMRLYLTIHSDHEggNVSAHTSHLVGSALSDPYLSFAA 262 chicken
2C6X_A    125 iayrkrwtrgeqaiapssqyGHVENYYYMltge-qpseAKKKALETYMILATEHGm-NASTFSARVTLSTESDLVSAVTA 202 Bacillus subtilis
2CTS_A    188 kiyrnlyregssigaidsklDWSHNFTNMlgy---tdaQFTELMRLYLTIHSDHEggNVSAHTSHLVGSALSDPYLSFAA 264 pig
2IFC_A    136 tvnvyrhimnmpaelpkpsdSYAESFLNAafgr-katkEEIDAMNTALILYTDHEv-PASTTAGLVAVSTLSDMYSGITA 213 Thermoplasma acido...
6CSC_A    188 kiyrnlyragssigaidsklDWSHNFTNMlgy---tdpQFTELMRLYLTIHSDHEggNVSAHTSHLVGSALSDPYLSFAA 264 chicken
6CTS_A    188 kiyrnlyragssigaidsklDWSHNFTNMlgy---tdaQFTELMRLYLTIHSDHEggNVSAHTSHLVGSALSDPYLSFAA 264 chicken
AAF09126  179 ayihyfkkeslyihfpdpelTTAENILRMlrpdchysdMEAKVLDIALILHMEHGggNNSTFTTHVVTSSGTDTYATIAA 258 Lactococcus lactis...
NP_104859 161 adaaraigvlagalgaeagpDPVHRRLARgws---vddAGADAIRRALVLLADHEl-NASTFAARVAASTGASPAACLLA 236 Mesorhizobium loti...
Feature 1            #### #  #                                      ########  #    #          
4CTS_A    265 AMNGLAGPLHGLANQEVLVWLTQLqkevgkd----vsdeklRDYIWNTLns-grVVPGYGHAVLRKTDPRYTCQREFALK 339 pig
1AMZ_A    263 AMNGLAGPLHGLANQEVLLWLSQLqkdlgad----asdeklRDYIWNTLns-grVVPGYGHAVLRKTDPRYTCQREFALK 337 chicken
1CSH_A    263 AMNGLAGPLHGLANQEVLLWLSQLqkdlgad----asdeklRDYIWNTLns-grVVPGYGHAVLRKTDPRYTCQREFALK 337 chicken
2C6X_A    203 ALGTMKGPLHGGAPSAVTKMLEDIgek-----------ehaEAYLKEKLek-geRLMGFGHRVYKTKDPRAEALRQKAEE 270 Bacillus subtilis
2CTS_A    265 AMNGLAGPLHGLANQEVLVWLTQLqkevgkd----vsdeklRDYIWNTLns-grVVPGYGHAVLRKTDPRYTCQREFALK 339 pig
2IFC_A    214 ALAALKGPLHGGAAEAAIAQFDEIkdp-----------amvEKWFNDNIingkkRLMGFGHRVYKTYDPRAKIFKGIAEK 282 Thermoplasma acido...
6CSC_A    265 AMNGLAGPLHGLANQEVLLWLSQLqkdlgad----asdeklRDYIWNTLns-grVVPGYGHAVLRKTDPRYTCQREFALK 339 chicken
6CTS_A    265 AMNGLAGPLHGLANQEVLGWLAQLqkaxxxa----gadaslRDYIWNTLns-grVVPGYGHAVLRKTDPRYTCQREFALK 339 chicken
AAF09126  259 ALSSLKGPKHGGANIKAAKMLENIkenisdynndeeikkylHQILNKEVfdkqgLIYGIGHAIYSVSDPRFEVFKSYVES 338 Lactococcus lactis...
NP_104859 237 GLATLSGPRHGGAGEAVMQLAEDAarh------------gaDAAIRRWLgh-drPLPAFGHPLYPDGDPRTTALSAAIPV 303 Mesorhizobium loti...
Feature 1                                        #  # #                      #   #            
4CTS_A    340 hlph----dpmFKLVAQLYKIVPNVlleqg-kaknPWPNVDAHSGVLLQYYGmte-mnYYTVLFGVSRALGVLAQLIWSR 413 pig
1AMZ_A    338 hlps----dpmFKLVAQLYKIVPNVlleqg-kaknPWPNVDAHSGVLLQYYGmte-mnYYTVLFGVSRALGVLAQLIWSR 411 chicken
1CSH_A    338 hlps----dpmFKLVAQLYKIVPNVlleqg-kaknPWPNVDAHSGVLLQYYGmte-mnYYTVLFGVSRALGVLAQLIWSR 411 chicken
2C6X_A    271 vagndrdldlaLHVEAEAIRLLEIYkpg-----rkLYTNVEFYAAAVMRAIDfd--deLFTPTFSASRMVGWCAHVLEQA 343 Bacillus subtilis
2CTS_A    340 hlph----dpmFKLVAQLYKIVPNVlleqg-kaknPWPNVDAHSGVLLQYYGmte-mnYYTVLFGVSRALGVLAQLIWSR 413 pig
2IFC_A    283 lsskkpevhkvYEIATKLEDFGIKAfgs-----kgIYPNTDYFSGIVYMSIGfplrnnIYTALFALSRVTGWQAHFIEYV 357 Thermoplasma acido...
6CSC_A    340 hlps----dpmFKLVAQLYKIVPNVlleqg-kaknPWPNVDAHSGVLLQYYGmte-mnYYTVLFGVSRALGVLAQLIWSR 413 chicken
6CTS_A    340 hlpg----dpmFKLVAQLYKIVPNVlleqg-aaanPWPNVDAHSGVLLQYYGmte-mnYYTVLFGVSRALGVLAQLIWSR 413 chicken
AAF09126  339 lakek-gleeeFKLYEKVAFLAPKVisenrkiyktICPNVDFYSGFVYKILEip--qeLFTPLFAIARIVGWLAHRMEEL 415 Lactococcus lactis...
NP_104859 304 -----------DETLQQLEKAAIAMt--------gARPNIDFALAALTRGLGlp--rdAPFQLFALGRSVGWAAHMVEQI 362 Mesorhizobium loti...
Feature 1         #  #     
4CTS_A    414 ALgfPLERPKSMS 426 pig
1AMZ_A    412 ALgfPLERPKSMS 424 chicken
1CSH_A    412 ALgfPLERPKSMS 424 chicken
2C6X_A    344 ENn-MIFRPSAQY 355 Bacillus subtilis
2CTS_A    414 ALgfPLERPKSMS 426 pig
2IFC_A    358 EEqqRLIRPRAVY 370 Thermoplasma acidophilum
6CSC_A    414 ALgfPLERPKSMS 426 chicken
6CTS_A    414 ALgfPLERPKSMS 426 chicken
AAF09126  416 INmnKIIRPAYES 428 Lactococcus lactis subsp. lactis
NP_104859 363 VSg-SIIRPRGRY 374 Mesorhizobium loti MAFF303099

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