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: 17-Jan-2013
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:
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1          #                                                                            
4CTS_A       43 GGMRGMK-----GLVYETsVLDPde--------gIRFRGYSIPECqkmlpkakggeeplPEGLFWLLVTGQIPtEEQVSW 109
1AMZ_A       41 GGMRGMK-----GLIYETsVLDPde--------gIRFRGFSIPECqkllpkagggeeplPEGLFWLLVTGQIPtPEQVSW 107
1CSH_A       41 GGMRGMK-----GLIYETsVLDPde--------gIRFRGFSIPECqkllpkagggeeplPEGLFWLLVTGQIPtPEQVSW 107
2CTS_A       43 GGMRGMK-----GLVYETsVLDPde--------gIRFRGYSIPECqkmlpkakggeeplPEGLFWLLVTGQIPtEEQVSW 109
2H12_A       52 PGYGETA-----ACNSKItFIDGdk-------gvLLHRGYPIAQLaen---------asYEEVIYLLLNGELPnKAQYDT 110
6CSC_A       43 GGMRGMK-----GLIYETsVLDPde--------gIRFRGFSIPECqkllpkagggeeplPEGLFWLLVTGQIPtPEQVSW 109
6CTS_A       43 GGMRGMK-----GLVYETsVLDPde--------gIRFRGFSIPECqkllpkggxggeplPEGLFWLLVTGQIPtGAQVSW 109
gi 6456029   28 KGLRDINgkgvlAGLTNIsAIHSfdkegnqipgvLEYRAYNIKDIvsdlrs---knrfgFEEMTYLLLFGELPsAKELQE 104
gi 15231130  97 PGYLNTA-----PVRSSIcYIDGde-------giLRYRGYPIEELaes---------stFIEVAYLLMYGNLPsQSQLAD 155
gi 78484695   5 PGLAGVP-----ATESEIsYIDGnk-------gvLTYRGYDIMELaey---------ssFEETTLLLLFGNLPtADELAD 63
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                       
4CTS_A      110 LSKEWAKRaaLPSHVVTMLdnfptnLHPMSQLSAAITALnsesnfarayaegihrtkyweliYEDCMDLIAKLPCVAAKI 189
1AMZ_A      108 VSKEWAKRaaLPSHVVTMLdnfptnLHPMSQLSAAITALnsesnfarayaeginrtkywefvYEDAMDLIAKLPCVAAKI 187
1CSH_A      108 VSKEWAKRaaLPSHVVTMLdnfptnLHPMSQLSAAITALnsesnfarayaeginrtkywefvYEDAMDLIAKLPCVAAKI 187
2CTS_A      110 LSKEWAKRaaLPSHVVTMLdnfptnLHPMSQLSAAITALnsesnfarayaegihrtkyweliYEDCMDLIAKLPCVAAKI 189
2H12_A      111 FTNTLTNHtlLHEQIRNFFngfrrdAHPMAILCGTVGALsafypdan-------diaipanrDLAAMRLIAKIPTIAAWA 183
6CSC_A      110 VSKEWAKRaaLPSHVVTMLdnfptnLHPMSQLSAAITALnsesnfarayaeginrtkywefvYEDAMDLIAKLPCVAAKI 189
6CTS_A      110 LSKEWAKRaaLPSHVVTMLdnfptnLHPMSQLSAAITALnsesnfarayaegilrtkywemvYESAMDLIAKLPCVAAKI 189
gi 6456029  105 FQILLASKrtLPEFFVRETiltnpsSDVMNSMSRCLLALasydkkas--------disienvLEQSLALIADFPLLAIYS 176
gi 15231130 156 WEFTVSQHsaVPQGVLDIIqsmphdAHPMGVLVSAMSALsifhpdanpalsgqdiykskqvrDKQIVRILGKAPTIAAAA 235
gi 78484695  64 FENKLRNArrVKYNLREIMknlpatTHPMHMLQVAVASLasfypsteym---kggtenqeyiNEVTVNIISHMGTLVAMW 140
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                  #   #                
4CTS_A      190 Yrnl----yreGSSIGAIDsklDWSHNFTNMlgy-------tdaQFTELMRLYLTIHSDHEggNVSAHTSHLVGSALSDP 258
1AMZ_A      188 Yrnl----yraGSSIGAIDsklDWSHNFTNMlgy-------tdpQFTELMRLYLTIHSDHEggNVSAHTSHLVGSALSDP 256
1CSH_A      188 Yrnl----yraGSSIGAIDsklDWSHNFTNMlgy-------tdpQFTELMRLYLTIHSDHEggNVSAHTSHLVGSALSDP 256
2CTS_A      190 Yrnl----yreGSSIGAIDsklDWSHNFTNMlgy-------tdaQFTELMRLYLTIHSDHEggNVSAHTSHLVGSALSDP 258
2H12_A      184 Yky------tqGEAFIYPRndlNYAENFLSMmfarmsepykvnpVLARAMNRILILHADHEq-NASTSTVRLAGSTGANP 256
6CSC_A      190 Yrnl----yraGSSIGAIDsklDWSHNFTNMlgy-------tdpQFTELMRLYLTIHSDHEggNVSAHTSHLVGSALSDP 258
6CTS_A      190 Yrnl----yraGSSIGAIDsklDWSHNFTNMlgy-------tdaQFTELMRLYLTIHSDHEggNVSAHTSHLVGSALSDP 258
gi 6456029  177 YqayihyfkkeSLYIHFPDpelTTAENILRMlrpdc----hysdMEAKVLDIALILHMEHGggNNSTFTTHVVTSSGTDT 252
gi 15231130 236 Ylr------taGRPPVLPSanlSYSENFLYMldsmgnrsykpnpRLARVLDILFILHAEHEm-NCSTAAARHLASSGVDV 308
gi 78484695 141 Ehm------rnGFDPIEPRkdlTYAENFLYMvtge-----epdkDWARLLDACLILHAEHTi-NASTFTTMVTGSTLANP 208
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                    #### #  #                                      ########  #    #    
4CTS_A      259 YLSFAAAMNGLAGPLHGLANQEVLVWLTQLqkevgkd----vsdeklRDYIWNTLns-grVVPGYGHAVLRKTDPRYTCQ 333
1AMZ_A      257 YLSFAAAMNGLAGPLHGLANQEVLLWLSQLqkdlgad----asdeklRDYIWNTLns-grVVPGYGHAVLRKTDPRYTCQ 331
1CSH_A      257 YLSFAAAMNGLAGPLHGLANQEVLLWLSQLqkdlgad----asdeklRDYIWNTLns-grVVPGYGHAVLRKTDPRYTCQ 331
2CTS_A      259 YLSFAAAMNGLAGPLHGLANQEVLVWLTQLqkevgkd----vsdeklRDYIWNTLns-grVVPGYGHAVLRKTDPRYTCQ 333
2H12_A      257 FACIAAGIAALWGPAHGGANEAVLKMLARIgkke---------nipaFIAQVKDKns-gvKLMGFGHRVYKNFDPRAKIM 326
6CSC_A      259 YLSFAAAMNGLAGPLHGLANQEVLLWLSQLqkdlgad----asdeklRDYIWNTLns-grVVPGYGHAVLRKTDPRYTCQ 333
6CTS_A      259 YLSFAAAMNGLAGPLHGLANQEVLGWLAQLqkaxxxa----gadaslRDYIWNTLns-grVVPGYGHAVLRKTDPRYTCQ 333
gi 6456029  253 YATIAAALSSLKGPKHGGANIKAAKMLENIkenisdynndeeikkylHQILNKEVfdkqgLIYGIGHAIYSVSDPRFEVF 332
gi 15231130 309 YTACAGAVGALYGPLHGGANEAVLKMLAEIgtae---------nipdFIEGVKNRk---rKMSGFGHRVYKNYDPRAKVI 376
gi 78484695 209 CSVISSAIASLSGPLHGGANQKVIEMLDEIgtp-----------enaRPYIEKRLae-kkVIWGMGHREYKTKDPRATIL 276
                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                   #  # #                     #   #    
4CTS_A      334 REFALKhlph-------dpmFKLVAQLYKIVPNVlleqg-kaknPWPNVDAHSGVLLQYYGmtemnYYTVLFGVSRALGV 405
1AMZ_A      332 REFALKhlps-------dpmFKLVAQLYKIVPNVlleqg-kaknPWPNVDAHSGVLLQYYGmtemnYYTVLFGVSRALGV 403
1CSH_A      332 REFALKhlps-------dpmFKLVAQLYKIVPNVlleqg-kaknPWPNVDAHSGVLLQYYGmtemnYYTVLFGVSRALGV 403
2CTS_A      334 REFALKhlph-------dpmFKLVAQLYKIVPNVlleqg-kaknPWPNVDAHSGVLLQYYGmtemnYYTVLFGVSRALGV 405
2H12_A      327 QQTCHEvltelg--ikddplLDLAVELEKIALSDdyfv---qrkLYPNVDFYSGIILKAMGip-tsMFTVLFAVARTTGW 400
6CSC_A      334 REFALKhlps-------dpmFKLVAQLYKIVPNVlleqg-kaknPWPNVDAHSGVLLQYYGmtemnYYTVLFGVSRALGV 405
6CTS_A      334 REFALKhlpg-------dpmFKLVAQLYKIVPNVlleqg-aaanPWPNVDAHSGVLLQYYGmtemnYYTVLFGVSRALGV 405
gi 6456029  333 KSYVESlakek----gleeeFKLYEKVAFLAPKVisenrkiyktICPNVDFYSGFVYKILEip-qeLFTPLFAIARIVGW 407
gi 15231130 377 KKLADEvfsiv----grdplIEVAVALEKAALSDeyfv---krkLYPNVDFYSGLIYRAMGfp-peFFTVLFAVPRMAGY 448
gi 78484695 277 QKLSSEllqnksdagslskaFETAMEVERVCEELlgh-----kgVYPNVDFYSGILYKEMGfd-agLFTPIFAVARSAGW 350
                       410       420
                ....*....|....*....|..
Feature 1                    #  #     
4CTS_A      406 LAQLIWSRALg-fPLERPKSMS 426
1AMZ_A      404 LAQLIWSRALg-fPLERPKSMS 424
1CSH_A      404 LAQLIWSRALg-fPLERPKSMS 424
2CTS_A      406 LAQLIWSRALg-fPLERPKSMS 426
2H12_A      401 VSQWKEMIEEpgqRISRPRQLY 422
6CSC_A      406 LAQLIWSRALg-fPLERPKSMS 426
6CTS_A      406 LAQLIWSRALg-fPLERPKSMS 426
gi 6456029  408 LAHRMEELINm-nKIIRPAYES 428
gi 15231130 449 LSHWRESLDDpdtRIMRPQQAY 470
gi 78484695 351 MAHWREQLQNn--KIFRPTQIY 370

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