4CTS,1A59,1AJ8,1AMZ,1CSH,1IXE,1NXG,1O7X,1VGP,2C6X,2CTS,2H12,2IBP,2IFC,2P2W,6CSC,6CTS


Conserved Protein Domain Family
citrate_synt_like_1

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cd06118: citrate_synt_like_1 
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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 are 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.
Statistics
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PSSM-Id: 99871
View PSSM: cd06118
Aligned: 33 rows
Threshold Bit Score: 408.914
Threshold Setting Gi: 50551811
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: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.
  • 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
  • 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:2C6X_A, Bacillus subtilis CS-I dimer bound with citrate, contacts at 3.5A
    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

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1               #                                                                            
4CTS_A            43 GGMRGMK-----GLVYETsVLDPde--------gIRFRGYSIPECqkmlpkakggeeplPEGLFWLLVTGQIPtEEQVSW 109 pig
1AMZ_A            41 GGMRGMK-----GLIYETsVLDPde--------gIRFRGFSIPECqkllpkagggeeplPEGLFWLLVTGQIPtPEQVSW 107 chicken
1CSH_A            41 GGMRGMK-----GLIYETsVLDPde--------gIRFRGFSIPECqkllpkagggeeplPEGLFWLLVTGQIPtPEQVSW 107 chicken
2CTS_A            43 GGMRGMK-----GLVYETsVLDPde--------gIRFRGYSIPECqkmlpkakggeeplPEGLFWLLVTGQIPtEEQVSW 109 pig
2H12_A            52 PGYGETA-----ACNSKItFIDGdk-------gvLLHRGYPIAQLaen---------asYEEVIYLLLNGELPnKAQYDT 110 Acetobacter...
6CSC_A            43 GGMRGMK-----GLIYETsVLDPde--------gIRFRGFSIPECqkllpkagggeeplPEGLFWLLVTGQIPtPEQVSW 109 chicken
6CTS_A            43 GGMRGMK-----GLVYETsVLDPde--------gIRFRGFSIPECqkllpkggxggeplPEGLFWLLVTGQIPtGAQVSW 109 chicken
AAF09126          28 KGLRDINgkgvlAGLTNIsAIHSfdkegnqipgvLEYRAYNIKDIvsdlrs---knrfgFEEMTYLLLFGELPsAKELQE 104 Lactococcus...
NP_191434         97 PGYLNTA-----PVRSSIcYIDGde-------giLRYRGYPIEELaes---------stFIEVAYLLMYGNLPsQSQLAD 155 thale cress
REF_jgi:Tcr_0350   5 PGLAGVP-----ATESEIsYIDGnk-------gvLTYRGYDIMELaey---------ssFEETTLLLLFGNLPtADELAD 63  Thiomicrosp...
Feature 1                                                                                            
4CTS_A           110 LSKEWAKRaaLPSHVVTMLdnfptnLHPMSQLSAAITALnsesnfarayaegihrtkyweliYEDCMDLIAKLPCVAAKI 189 pig
1AMZ_A           108 VSKEWAKRaaLPSHVVTMLdnfptnLHPMSQLSAAITALnsesnfarayaeginrtkywefvYEDAMDLIAKLPCVAAKI 187 chicken
1CSH_A           108 VSKEWAKRaaLPSHVVTMLdnfptnLHPMSQLSAAITALnsesnfarayaeginrtkywefvYEDAMDLIAKLPCVAAKI 187 chicken
2CTS_A           110 LSKEWAKRaaLPSHVVTMLdnfptnLHPMSQLSAAITALnsesnfarayaegihrtkyweliYEDCMDLIAKLPCVAAKI 189 pig
2H12_A           111 FTNTLTNHtlLHEQIRNFFngfrrdAHPMAILCGTVGALsafypdan-------diaipanrDLAAMRLIAKIPTIAAWA 183 Acetobacter...
6CSC_A           110 VSKEWAKRaaLPSHVVTMLdnfptnLHPMSQLSAAITALnsesnfarayaeginrtkywefvYEDAMDLIAKLPCVAAKI 189 chicken
6CTS_A           110 LSKEWAKRaaLPSHVVTMLdnfptnLHPMSQLSAAITALnsesnfarayaegilrtkywemvYESAMDLIAKLPCVAAKI 189 chicken
AAF09126         105 FQILLASKrtLPEFFVRETiltnpsSDVMNSMSRCLLALasydkkas--------disienvLEQSLALIADFPLLAIYS 176 Lactococcus...
NP_191434        156 WEFTVSQHsaVPQGVLDIIqsmphdAHPMGVLVSAMSALsifhpdanpalsgqdiykskqvrDKQIVRILGKAPTIAAAA 235 thale cress
REF_jgi:Tcr_0350  64 FENKLRNArrVKYNLREIMknlpatTHPMHMLQVAVASLasfypsteym---kggtenqeyiNEVTVNIISHMGTLVAMW 140 Thiomicrosp...
Feature 1                                                                       #   #                
4CTS_A           190 Yrnl----yreGSSIGAIDsklDWSHNFTNMlgy-------tdaQFTELMRLYLTIHSDHEggNVSAHTSHLVGSALSDP 258 pig
1AMZ_A           188 Yrnl----yraGSSIGAIDsklDWSHNFTNMlgy-------tdpQFTELMRLYLTIHSDHEggNVSAHTSHLVGSALSDP 256 chicken
1CSH_A           188 Yrnl----yraGSSIGAIDsklDWSHNFTNMlgy-------tdpQFTELMRLYLTIHSDHEggNVSAHTSHLVGSALSDP 256 chicken
2CTS_A           190 Yrnl----yreGSSIGAIDsklDWSHNFTNMlgy-------tdaQFTELMRLYLTIHSDHEggNVSAHTSHLVGSALSDP 258 pig
2H12_A           184 Yky------tqGEAFIYPRndlNYAENFLSMmfarmsepykvnpVLARAMNRILILHADHEq-NASTSTVRLAGSTGANP 256 Acetobacter...
6CSC_A           190 Yrnl----yraGSSIGAIDsklDWSHNFTNMlgy-------tdpQFTELMRLYLTIHSDHEggNVSAHTSHLVGSALSDP 258 chicken
6CTS_A           190 Yrnl----yraGSSIGAIDsklDWSHNFTNMlgy-------tdaQFTELMRLYLTIHSDHEggNVSAHTSHLVGSALSDP 258 chicken
AAF09126         177 YqayihyfkkeSLYIHFPDpelTTAENILRMlrpdc----hysdMEAKVLDIALILHMEHGggNNSTFTTHVVTSSGTDT 252 Lactococcus...
NP_191434        236 Ylr------taGRPPVLPSanlSYSENFLYMldsmgnrsykpnpRLARVLDILFILHAEHEm-NCSTAAARHLASSGVDV 308 thale cress
REF_jgi:Tcr_0350 141 Ehm------rnGFDPIEPRkdlTYAENFLYMvtge-----epdkDWARLLDACLILHAEHTi-NASTFTTMVTGSTLANP 208 Thiomicrosp...
Feature 1                         #### #  #                                      ########  #    #    
4CTS_A           259 YLSFAAAMNGLAGPLHGLANQEVLVWLTQLqkevgkd----vsdeklRDYIWNTLns-grVVPGYGHAVLRKTDPRYTCQ 333 pig
1AMZ_A           257 YLSFAAAMNGLAGPLHGLANQEVLLWLSQLqkdlgad----asdeklRDYIWNTLns-grVVPGYGHAVLRKTDPRYTCQ 331 chicken
1CSH_A           257 YLSFAAAMNGLAGPLHGLANQEVLLWLSQLqkdlgad----asdeklRDYIWNTLns-grVVPGYGHAVLRKTDPRYTCQ 331 chicken
2CTS_A           259 YLSFAAAMNGLAGPLHGLANQEVLVWLTQLqkevgkd----vsdeklRDYIWNTLns-grVVPGYGHAVLRKTDPRYTCQ 333 pig
2H12_A           257 FACIAAGIAALWGPAHGGANEAVLKMLARIgkke---------nipaFIAQVKDKns-gvKLMGFGHRVYKNFDPRAKIM 326 Acetobacter...
6CSC_A           259 YLSFAAAMNGLAGPLHGLANQEVLLWLSQLqkdlgad----asdeklRDYIWNTLns-grVVPGYGHAVLRKTDPRYTCQ 333 chicken
6CTS_A           259 YLSFAAAMNGLAGPLHGLANQEVLGWLAQLqkaxxxa----gadaslRDYIWNTLns-grVVPGYGHAVLRKTDPRYTCQ 333 chicken
AAF09126         253 YATIAAALSSLKGPKHGGANIKAAKMLENIkenisdynndeeikkylHQILNKEVfdkqgLIYGIGHAIYSVSDPRFEVF 332 Lactococcus...
NP_191434        309 YTACAGAVGALYGPLHGGANEAVLKMLAEIgtae---------nipdFIEGVKNRk---rKMSGFGHRVYKNYDPRAKVI 376 thale cress
REF_jgi:Tcr_0350 209 CSVISSAIASLSGPLHGGANQKVIEMLDEIgtp-----------enaRPYIEKRLae-kkVIWGMGHREYKTKDPRATIL 276 Thiomicrosp...
Feature 1                                                        #  # #                     #   #    
4CTS_A           334 REFALKhlph-------dpmFKLVAQLYKIVPNVlleqg-kaknPWPNVDAHSGVLLQYYGmtemnYYTVLFGVSRALGV 405 pig
1AMZ_A           332 REFALKhlps-------dpmFKLVAQLYKIVPNVlleqg-kaknPWPNVDAHSGVLLQYYGmtemnYYTVLFGVSRALGV 403 chicken
1CSH_A           332 REFALKhlps-------dpmFKLVAQLYKIVPNVlleqg-kaknPWPNVDAHSGVLLQYYGmtemnYYTVLFGVSRALGV 403 chicken
2CTS_A           334 REFALKhlph-------dpmFKLVAQLYKIVPNVlleqg-kaknPWPNVDAHSGVLLQYYGmtemnYYTVLFGVSRALGV 405 pig
2H12_A           327 QQTCHEvltelg--ikddplLDLAVELEKIALSDdyfv---qrkLYPNVDFYSGIILKAMGip-tsMFTVLFAVARTTGW 400 Acetobacter...
6CSC_A           334 REFALKhlps-------dpmFKLVAQLYKIVPNVlleqg-kaknPWPNVDAHSGVLLQYYGmtemnYYTVLFGVSRALGV 405 chicken
6CTS_A           334 REFALKhlpg-------dpmFKLVAQLYKIVPNVlleqg-aaanPWPNVDAHSGVLLQYYGmtemnYYTVLFGVSRALGV 405 chicken
AAF09126         333 KSYVESlakek----gleeeFKLYEKVAFLAPKVisenrkiyktICPNVDFYSGFVYKILEip-qeLFTPLFAIARIVGW 407 Lactococcus...
NP_191434        377 KKLADEvfsiv----grdplIEVAVALEKAALSDeyfv---krkLYPNVDFYSGLIYRAMGfp-peFFTVLFAVPRMAGY 448 thale cress
REF_jgi:Tcr_0350 277 QKLSSEllqnksdagslskaFETAMEVERVCEELlgh-----kgVYPNVDFYSGILYKEMGfd-agLFTPIFAVARSAGW 350 Thiomicrosp...
Feature 1                         #  #     
4CTS_A           406 LAQLIWSRALg-fPLERPKSMS 426 pig
1AMZ_A           404 LAQLIWSRALg-fPLERPKSMS 424 chicken
1CSH_A           404 LAQLIWSRALg-fPLERPKSMS 424 chicken
2CTS_A           406 LAQLIWSRALg-fPLERPKSMS 426 pig
2H12_A           401 VSQWKEMIEEpgqRISRPRQLY 422 Acetobacter aceti
6CSC_A           406 LAQLIWSRALg-fPLERPKSMS 426 chicken
6CTS_A           406 LAQLIWSRALg-fPLERPKSMS 426 chicken
AAF09126         408 LAHRMEELINm-nKIIRPAYES 428 Lactococcus lactis subsp. lactis
NP_191434        449 LSHWRESLDDpdtRIMRPQQAY 470 thale cress
REF_jgi:Tcr_0350 351 MAHWREQLQNn--KIFRPTQIY 370 Thiomicrospira crunogena XCL-2

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