4CTS,1AMZ,1CSH,2CTS,6CSC,6CTS


Conserved Protein Domain Family
ScCS-like

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cd06103: ScCS-like 
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Saccharomyces cerevisiae (Sc) citrate synthase (CS)-like. CS catalyzes the condensation of acetyl coenzyme A (AcCoA) with oxaloacetate (OAA) to form citrate and coenzyme A (CoA), the first step in the citric acid cycle (TCA or Krebs cycle). Some CS proteins function as 2-methylcitrate synthase (2MCS). 2MCS catalyzes the condensation of propionyl-coenzyme A (PrCoA) and OAA to form 2-methylcitrate and CoA during propionate metabolism. 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). This group includes three S. cerevisiae CS proteins, ScCit1,-2,-3. ScCit1 is a nuclear-encoded mitochondrial CS with highly specificity for AcCoA; in addition to having activity with AcCoA, it plays a part in the construction of the TCA cycle metabolon. Yeast cells deleted for Cit1 are hyper-susceptible to apoptosis induced by heat and aging stress. ScCit2 is a peroxisomal CS involved in the glyoxylate cycle; in addition to having activity with AcCoA, it may have activity with PrCoA. ScCit3 is a mitochondrial CS and functions in the metabolism of PrCoA; it is a dual specificity CS and 2MCS, having similar catalytic efficiency with both AcCoA and PrCoA. The pattern of expression of the ScCIT3 gene follows that of the ScCIT1 gene and its expression is increased in the presence of a ScCIT1 deletion. Included in this group is the Tetrahymena 14 nm filament protein which functions as a CS in mitochondria and as a cytoskeletal component in cytoplasm and Geobacter sulfurreducens (GSu) CS. GSuCS is dimeric and eukaryotic-like; it lacks 2MCS activity and is inhibited by ATP. In contrast to eukaryotic and other prokaryotic CSs, GSuCIT is not stimulated by K+ ions. 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.
Statistics
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PSSM-Id: 99857
View PSSM: cd06103
Aligned: 17 rows
Threshold Bit Score: 727.557
Threshold Setting Gi: 124802537
Created: 18-Oct-2007
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
  • Citation:PMID 9254593

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                #                                       
4CTS_A         6 LKDILADLIPKEQARIKTFRQQHGntvVGQITVDMMYGGMRGMKGLVYETSVLDPDEGIRFRGYSIPECqkmLPKAKGGe 85  pig
6CSC_A         6 LKDVLASLIPKEQARIKTFRQQHGntaVGQITVDMSYGGMRGMKGLIYETSVLDPDEGIRFRGFSIPECqklLPKAGGGe 85  chicken
116475        26 LKKVIAEIIPQKQAELKEVKEKYGdkvVGQYTVKQVIGGMRGMKGLMSDLSRCDPYQGIIFRGYTIPQLkefLPKADPKa 105 Tetrahymena the...
NP_650152     33 LKAKLAKKIPIEREKFLGIKCLHGkkiIGQISVNSVIGGMRGLPLLFCETSSLDKNKGIYYRGKLLKDVcakLPRVQEGt 112 fruit fly
AAS67341       3 LKETLKQKIEEHRPRTTRLVKEFGkviIDQVTIDQCIGGARDIRCLVTDISYLDPQEGIRFRGKTIPETfeaLPKAAGSd 82  Geobacter sulfu...
XP_503380     26 LKGALKEAIPAKLELFKKVKSEYSqksLGDCKVENLLGGMRGLKCMLWEGSVLDADEGIRFHGKTIKECqevLPKAVEGg 105 Yarrowia lipoly...
XP_827827     40 LKLSILKKHQSDAPRIKQLIAKHGgdkLSESTVSSMYGGMRGVTGFVYEPSYLDKEVGIRFRGLTISECcekLPKSWRGg 119 Trypanosoma bru...
Q4QDX3        25 MKEQMLRRWKEDQKKIDDLRKKHGhekLCDATIDAVYGGMRGITGLVYEPSLLDPAEGIRFRGLTILECqemLPKAPGGk 104 Leishmania major
XP_952049    236 LMDKVERLVNVKREKLAELHNKYAdrrLGEVTLSMLFSGLKDVPAMVTETSELDPYKGIRFRGLTVDEMlsvLPGKNPDc 315 Theileria annul...
XP_001021439  25 LKTVLREQIPIKIQGFNEMKKKYGdrvMGEITVNQALGGMRGIRALFYDQSTVDPIDGVMFRGYSIPELhelLPKLRKPs 104 Tetrahymena the...
Feature 1                                                                                        
4CTS_A        86 --------ePLPEGLFWLLVTGQIPTEEQVSWLSKEWAKRa--aLPSHVVTMLDNFPTNLHPMSQLSAAITALNSESNFA 155 pig
6CSC_A        86 --------ePLPEGLFWLLVTGQIPTPEQVSWVSKEWAKRa--aLPSHVVTMLDNFPTNLHPMSQLSAAITALNSESNFA 155 chicken
116475       106 adq--anqePLPEGIFWLLMTGQLPTHAQVDALKHEWQNRg--tVNQDCVNFILNLPKDLHSMTMLSMALLYLQKDSKFA 181 Tetrahymena the...
NP_650152    113 q-------eGTPEGCFFLLTSGSMPTKKEAQEVTNEWLKRg--sVPRYCLRMIDSMDKRVHPMAQLCAASACLNPQSQFV 183 fruit fly
AAS67341      83 --------yPTVESFWYFLLTGEVPTQAQVDEVVAEWKVRq--eVPQYVFDAIRALPRDSHPMVMLSVGILALQKDSKFA 152 Geobacter sulfu...
XP_503380    106 --------eMLPESMLWFLFTGKVPTEEQVRGLSRELAEKg--eVPEFVNKMLDNLPPTLHPMTQFSMAVSALNHDSKFA 175 Yarrowia lipoly...
XP_827827    120 s-------sPLPEGMLWLLVTGTIPNERQVKEMHEELHRRaderAISAAVKTIASLPDNSHPMTQFGAGLMALQTYSKFA 192 Trypanosoma bru...
Q4QDX3       105 --------ePLPEAMFWLLMTGEVPTEEQVRGLNAELHRRadpeAIAAAQKAIAALPRNAHPMTAFSVGVLALQSYSKFA 176 Leishmania major
XP_952049    316 ---------PYTESVLWFLLTGEVPSPVDVDDLSYELYKRs--vVPDHVYKVIDGFPRDTHPMTQYITAISALQTESVFR 384 Theileria annul...
XP_001021439 105 aedfqsdqqPLPEGLFFLLLTGELPSYHQVELIRHEWDVRg--kVSDELINFINRLDNKMHPMTMLSLAILYEQKTSKFA 182 Tetrahymena the...
Feature 1                                                                                        
4CTS_A       156 RAYAEG-IHRTKYWELIYEDCMDLIAKLPCVAAKIYRNly---reGSSIGAIDsklDWSHNFTNMLGYtd-aQFTELMRL 230 pig
6CSC_A       156 RAYAEG-INRTKYWEFVYEDAMDLIAKLPCVAAKIYRNly---raGSSIGAIDsklDWSHNFTNMLGYtd-pQFTELMRL 230 chicken
116475       182 KLYDEGkISKKDYWEPFYEDSMDLIAKIPRVAAIIYRHky----rDSKLIDSDsklDWAGNYAHMMGFeq-hVVKECIRG 256 Tetrahymena the...
NP_650152    184 EAYTKG-ARRADYWKYSYEDSMNLIAMLPTVAAAIYSNvf---rdGEGSREVNyeeDWSGNFCRMLGLpe-kDFVDLMRL 258 fruit fly
AAS67341     153 GFYNSGkFNKMTAWEYVYEDAYDLVARIPVIAAFIYNLky----kGDKQLPIDpsaDCGANFARMIGQc--kEYEDVARM 226 Geobacter sulfu...
XP_503380    176 KAYERG-IPKSEYWEYTFDDSIDLIAKLPQIAAKIYQNsyl--ggGPLPGKIDlnrDWSYNYAAMMGKgdetGFVDLLRL 252 Yarrowia lipoly...
XP_827827    193 TAYSQGkANKTNYWEYALDDSLDLIARSSHVAAIVYNRlat--gkAQLANPSDpnlDWAANFTNMLGYkd-eSFWDCMRL 269 Trypanosoma bru...
Q4QDX3       177 AAYAAGkSNKKTYWEYALEDSLDMLARTPTVAAMIYNRetk--gqVELAAPSNsdlDWAANFAKMMGYqd-eEFWECMRL 253 Leishmania major
XP_952049    385 EAYFDKtYHKDTCWKLALEDCLNLFAKNSVVVGYIYRRsfldentKPEDVQYNsslDYAANLAHFLGNkt-eLFSDVMRL 463 Theileria annul...
XP_001021439 183 QLYNESkLNKSNYWEYTYEDSVDLIAKLPRIAATIYRKkf----kDGKPIAHKdglDWSAQLAHMMGFegqeTLNELLRA 258 Tetrahymena the...
Feature 1               #   #                             #### #  #                              
4CTS_A       231 YLTIHSDHEGGNVSAHTSHLVGSALSDPYLSFAAAMNGLAGPLHGLANQEVLVWLTQLqk---evGKDVSde------kL 301 pig
6CSC_A       231 YLTIHSDHEGGNVSAHTSHLVGSALSDPYLSFAAAMNGLAGPLHGLANQEVLLWLSQLqk---dlGADASde------kL 301 chicken
116475       257 YLSIHCDHEGGNVSAHTTHLVGSALSDPYLSYSAGVNGLAGPLHGLANQEVLKWLLQFie---ekGTKVSdk------dI 327 Tetrahymena the...
NP_650152    259 YMILHADHESGNVSAHACHLVGTALSDPFLSFSASMCGLAGPLHGLANQEVLVWLTKLrk---aiGDDPSde------eL 329 fruit fly
AAS67341     227 YFILHSDHESGNVSAHTTHLVHSALSDPYYAYSAGLNGLAGPLHGLANQEVLDWTIKFqek-yckDVEPTke------lV 299 Geobacter sulfu...
XP_503380    253 YFALHGDHEGGNVSAHATHLVGSALSDPYLSYSAGLQGLAGPLHGLAAQEVLRFILDMek---nvPKGYSne------dL 323 Yarrowia lipoly...
XP_827827    270 YLCLHADHEGGNVSAHATVLVASALSDPYLSLVAGLAGLAGPLHGLANQEVLTYLFEMrdk-ckaAGVDLhdrkrlaaeL 348 Trypanosoma bru...
Q4QDX3       254 YLSVHADHEGGNVSAHTTTLVASALSDPYLAFSAGLNGLAGPLHGLANQEVLNYLLSMqervkadGVNMHdeaa-lekaL 332 Leishmania major
XP_952049    464 YLALHSDHEGGNVSAHASHLVGSALADPYFCFSSALCGLSGPLHGMANQECLVWIKKMlsd--mgDKEVTvd------eV 535 Theileria annul...
XP_001021439 259 FLTIHADHEGGEVSTHASHLVGSALGDPYLCMTTAYTGLAGPLHGLANQEVLKWILNFve---vhGYDVTnr------qI 329 Tetrahymena the...
Feature 1                    ########  #    #                                          #  # #    
4CTS_A       302 RDYIWNTLNSGRVVPGYGHAVLRKTDPRYTCQREFALKHLp--hDPMFKLVAQLYKIVPNVLLEQGKAKNPWPNVDAHSG 379 pig
6CSC_A       302 RDYIWNTLNSGRVVPGYGHAVLRKTDPRYTCQREFALKHLp--sDPMFKLVAQLYKIVPNVLLEQGKAKNPWPNVDAHSG 379 chicken
116475       328 EDYVDHVISSGRVVPGYGHAVLRDTDPRFHHQVDFSKFHLk--dDQMIKLLHQCADVIPKKLLTYKKIANPYPNVDCHSG 405 Tetrahymena the...
NP_650152    330 KKFIDDTLKGGQVIPGYGHAVLRDTDPRFVLQNEFAMKHCk--dDPGVKLVTRLWKIIPEVLKKLNKVANPYPNVDAHSG 407 fruit fly
AAS67341     300 TKALWDTLNAGQVVPGYGHAVLRKTDPRYTSQREFCLKTPglkdDPLFKLVAMIFETAPGVLMEHGKAKNPWPNVDAQSG 379 Geobacter sulfu...
XP_503380    324 VKYLWSVLKSGRVIPGYGHAVLRKPDPRFEALMNFANSRQeirdDPVFQLVSRTSEVATGVLTEHGKTKNPHPNVDSSSG 403 Yarrowia lipoly...
XP_827827    349 EKLTWDVLNAKRVVPGYGHAVLGMTDPRYTCFREYCKNNFp--nDELFILVDAIYEIMPGILKKHGKVRNPFPNVDAQSG 426 Trypanosoma bru...
Q4QDX3       333 SNYTWELLNSGQVVPGYGHAVLRKVDPRYTCQRNFCLRHKf--dDDLFKLVNTIYSIMPGILKEHGKTKNPYPNVDAHSG 410 Leishmania major
XP_952049    536 KKYAEDTMAKKQVIPGYGHAVLKVTDPRHTAFVRFALKHFp--dDPLVKLLDTCLKAIPEVLKASGKVRNPNPNVDCSTG 613 Theileria annul...
XP_001021439 330 EDYVNTTVLSGRLVPGYGHAVLRRPDPRFLHLYDFGNKYLr--dNEMIRLLHQMTDVIPRRLRTFKNISSPYPNVDCHSG 407 Tetrahymena the...
Feature 1                         #   #                #  #         
4CTS_A       380 VLLQYYGMTEMNYYTVLFGVSRALGVLAQLIWSRALGFPLERPKSMSTDGL 430 pig
6CSC_A       380 VLLQYYGMTEMNYYTVLFGVSRALGVLAQLIWSRALGFPLERPKSMSTAGL 430 chicken
116475       406 VLLYSLGLTEYQYYTVVFAVSRALGCMANLIWSRAFGLPIERPGSADLKWF 456 Tetrahymena thermophila
NP_650152    408 VLLQHYCLKELKFYTVLFGVSRALGVLSQLIWSRALGAPIERPKSFSSIEI 458 fruit fly
AAS67341     380 VIQWYYGLREWDFYTVLFGVGRALGCMANITWDRGLGYAIERPKSVTTPML 430 Geobacter sulfurreducens
XP_503380    404 VLFHHYGIHETLYYTVTFGVSRALGPLPQLVWDRILGLPIERPKSLSLEEI 454 Yarrowia lipolytica CLIB122
XP_827827    427 VLLQHYGMKEQLFYTVLFGLSRQLGVLTGIVWDRLQGRPIERPKTMTSESL 477 Trypanosoma brucei TREU927
Q4QDX3       411 VLLQHYGLTEQNYYTVLFGLSRQMGVLAGVVWDRLQGRPLERPKSITTEML 461 Leishmania major
XP_952049    614 VLLSHFNVDQPQIFTVLFGLSRSMGILSQLVWARALRYPIERPKSLSLETV 664 Theileria annulata strain Ankara
XP_001021439 408 ALLYQLGIQEYQFYTVLFAISRSIGCLTNLVWCRAFGLPIERPESADLAYY 458 Tetrahymena thermophila SB210

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