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: 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
  • 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         6 LKDILADLIPKEQARIKTFRQQHGntvVGQITVDMMYGGMRGMKGLVYETSVLDPDEGIRFRGYSIPECqkmLPKAKGGe 85
6CSC_A         6 LKDVLASLIPKEQARIKTFRQQHGntaVGQITVDMSYGGMRGMKGLIYETSVLDPDEGIRFRGFSIPECqklLPKAGGGe 85
gi 116475     26 LKKVIAEIIPQKQAELKEVKEKYGdkvVGQYTVKQVIGGMRGMKGLMSDLSRCDPYQGIIFRGYTIPQLkefLPKADPKa 105
gi 21356863   33 LKAKLAKKIPIEREKFLGIKCLHGkkiIGQISVNSVIGGMRGLPLLFCETSSLDKNKGIYYRGKLLKDVcakLPRVQEGt 112
gi 45544838    3 LKETLKQKIEEHRPRTTRLVKEFGkviIDQVTIDQCIGGARDIRCLVTDISYLDPQEGIRFRGKTIPETfeaLPKAAGSd 82
gi 50551811   26 LKGALKEAIPAKLELFKKVKSEYSqksLGDCKVENLLGGMRGLKCMLWEGSVLDADEGIRFHGKTIKECqevLPKAVEGg 105
gi 71748976   40 LKLSILKKHQSDAPRIKQLIAKHGgdkLSESTVSSMYGGMRGVTGFVYEPSYLDKEVGIRFRGLTISECcekLPKSWRGg 119
gi 75034916   25 MKEQMLRRWKEDQKKIDDLRKKHGhekLCDATIDAVYGGMRGITGLVYEPSLLDPAEGIRFRGLTILECqemLPKAPGGk 104
gi 84994654  236 LMDKVERLVNVKREKLAELHNKYAdrrLGEVTLSMLFSGLKDVPAMVTETSELDPYKGIRFRGLTVDEMlsvLPGKNPDc 315
gi 118376514  25 LKTVLREQIPIKIQGFNEMKKKYGdrvMGEITVNQALGGMRGIRALFYDQSTVDPIDGVMFRGYSIPELhelLPKLRKPs 104
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
4CTS_A        86 --------ePLPEGLFWLLVTGQIPTEEQVSWLSKEWAKRa--aLPSHVVTMLDNFPTNLHPMSQLSAAITALNSESNFA 155
6CSC_A        86 --------ePLPEGLFWLLVTGQIPTPEQVSWVSKEWAKRa--aLPSHVVTMLDNFPTNLHPMSQLSAAITALNSESNFA 155
gi 116475    106 adq--anqePLPEGIFWLLMTGQLPTHAQVDALKHEWQNRg--tVNQDCVNFILNLPKDLHSMTMLSMALLYLQKDSKFA 181
gi 21356863  113 q-------eGTPEGCFFLLTSGSMPTKKEAQEVTNEWLKRg--sVPRYCLRMIDSMDKRVHPMAQLCAASACLNPQSQFV 183
gi 45544838   83 --------yPTVESFWYFLLTGEVPTQAQVDEVVAEWKVRq--eVPQYVFDAIRALPRDSHPMVMLSVGILALQKDSKFA 152
gi 50551811  106 --------eMLPESMLWFLFTGKVPTEEQVRGLSRELAEKg--eVPEFVNKMLDNLPPTLHPMTQFSMAVSALNHDSKFA 175
gi 71748976  120 s-------sPLPEGMLWLLVTGTIPNERQVKEMHEELHRRaderAISAAVKTIASLPDNSHPMTQFGAGLMALQTYSKFA 192
gi 75034916  105 --------ePLPEAMFWLLMTGEVPTEEQVRGLNAELHRRadpeAIAAAQKAIAALPRNAHPMTAFSVGVLALQSYSKFA 176
gi 84994654  316 ---------PYTESVLWFLLTGEVPSPVDVDDLSYELYKRs--vVPDHVYKVIDGFPRDTHPMTQYITAISALQTESVFR 384
gi 118376514 105 aedfqsdqqPLPEGLFFLLLTGELPSYHQVELIRHEWDVRg--kVSDELINFINRLDNKMHPMTMLSLAILYEQKTSKFA 182
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
4CTS_A       156 RAYAEG-IHRTKYWELIYEDCMDLIAKLPCVAAKIYRNly---reGSSIGAIDsklDWSHNFTNMLGYtd-aQFTELMRL 230
6CSC_A       156 RAYAEG-INRTKYWEFVYEDAMDLIAKLPCVAAKIYRNly---raGSSIGAIDsklDWSHNFTNMLGYtd-pQFTELMRL 230
gi 116475    182 KLYDEGkISKKDYWEPFYEDSMDLIAKIPRVAAIIYRHky----rDSKLIDSDsklDWAGNYAHMMGFeq-hVVKECIRG 256
gi 21356863  184 EAYTKG-ARRADYWKYSYEDSMNLIAMLPTVAAAIYSNvf---rdGEGSREVNyeeDWSGNFCRMLGLpe-kDFVDLMRL 258
gi 45544838  153 GFYNSGkFNKMTAWEYVYEDAYDLVARIPVIAAFIYNLky----kGDKQLPIDpsaDCGANFARMIGQc--kEYEDVARM 226
gi 50551811  176 KAYERG-IPKSEYWEYTFDDSIDLIAKLPQIAAKIYQNsyl--ggGPLPGKIDlnrDWSYNYAAMMGKgdetGFVDLLRL 252
gi 71748976  193 TAYSQGkANKTNYWEYALDDSLDLIARSSHVAAIVYNRlat--gkAQLANPSDpnlDWAANFTNMLGYkd-eSFWDCMRL 269
gi 75034916  177 AAYAAGkSNKKTYWEYALEDSLDMLARTPTVAAMIYNRetk--gqVELAAPSNsdlDWAANFAKMMGYqd-eEFWECMRL 253
gi 84994654  385 EAYFDKtYHKDTCWKLALEDCLNLFAKNSVVVGYIYRRsfldentKPEDVQYNsslDYAANLAHFLGNkt-eLFSDVMRL 463
gi 118376514 183 QLYNESkLNKSNYWEYTYEDSVDLIAKLPRIAATIYRKkf----kDGKPIAHKdglDWSAQLAHMMGFegqeTLNELLRA 258
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1               #   #                             #### #  #                              
4CTS_A       231 YLTIHSDHEGGNVSAHTSHLVGSALSDPYLSFAAAMNGLAGPLHGLANQEVLVWLTQLqk---evGKDVSde------kL 301
6CSC_A       231 YLTIHSDHEGGNVSAHTSHLVGSALSDPYLSFAAAMNGLAGPLHGLANQEVLLWLSQLqk---dlGADASde------kL 301
gi 116475    257 YLSIHCDHEGGNVSAHTTHLVGSALSDPYLSYSAGVNGLAGPLHGLANQEVLKWLLQFie---ekGTKVSdk------dI 327
gi 21356863  259 YMILHADHESGNVSAHACHLVGTALSDPFLSFSASMCGLAGPLHGLANQEVLVWLTKLrk---aiGDDPSde------eL 329
gi 45544838  227 YFILHSDHESGNVSAHTTHLVHSALSDPYYAYSAGLNGLAGPLHGLANQEVLDWTIKFqek-yckDVEPTke------lV 299
gi 50551811  253 YFALHGDHEGGNVSAHATHLVGSALSDPYLSYSAGLQGLAGPLHGLAAQEVLRFILDMek---nvPKGYSne------dL 323
gi 71748976  270 YLCLHADHEGGNVSAHATVLVASALSDPYLSLVAGLAGLAGPLHGLANQEVLTYLFEMrdk-ckaAGVDLhdrkrlaaeL 348
gi 75034916  254 YLSVHADHEGGNVSAHTTTLVASALSDPYLAFSAGLNGLAGPLHGLANQEVLNYLLSMqervkadGVNMHdeaa-lekaL 332
gi 84994654  464 YLALHSDHEGGNVSAHASHLVGSALADPYFCFSSALCGLSGPLHGMANQECLVWIKKMlsd--mgDKEVTvd------eV 535
gi 118376514 259 FLTIHADHEGGEVSTHASHLVGSALGDPYLCMTTAYTGLAGPLHGLANQEVLKWILNFve---vhGYDVTnr------qI 329
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                    ########  #    #                                          #  # #    
4CTS_A       302 RDYIWNTLNSGRVVPGYGHAVLRKTDPRYTCQREFALKHLp--hDPMFKLVAQLYKIVPNVLLEQGKAKNPWPNVDAHSG 379
6CSC_A       302 RDYIWNTLNSGRVVPGYGHAVLRKTDPRYTCQREFALKHLp--sDPMFKLVAQLYKIVPNVLLEQGKAKNPWPNVDAHSG 379
gi 116475    328 EDYVDHVISSGRVVPGYGHAVLRDTDPRFHHQVDFSKFHLk--dDQMIKLLHQCADVIPKKLLTYKKIANPYPNVDCHSG 405
gi 21356863  330 KKFIDDTLKGGQVIPGYGHAVLRDTDPRFVLQNEFAMKHCk--dDPGVKLVTRLWKIIPEVLKKLNKVANPYPNVDAHSG 407
gi 45544838  300 TKALWDTLNAGQVVPGYGHAVLRKTDPRYTSQREFCLKTPglkdDPLFKLVAMIFETAPGVLMEHGKAKNPWPNVDAQSG 379
gi 50551811  324 VKYLWSVLKSGRVIPGYGHAVLRKPDPRFEALMNFANSRQeirdDPVFQLVSRTSEVATGVLTEHGKTKNPHPNVDSSSG 403
gi 71748976  349 EKLTWDVLNAKRVVPGYGHAVLGMTDPRYTCFREYCKNNFp--nDELFILVDAIYEIMPGILKKHGKVRNPFPNVDAQSG 426
gi 75034916  333 SNYTWELLNSGQVVPGYGHAVLRKVDPRYTCQRNFCLRHKf--dDDLFKLVNTIYSIMPGILKEHGKTKNPYPNVDAHSG 410
gi 84994654  536 KKYAEDTMAKKQVIPGYGHAVLKVTDPRHTAFVRFALKHFp--dDPLVKLLDTCLKAIPEVLKASGKVRNPNPNVDCSTG 613
gi 118376514 330 EDYVNTTVLSGRLVPGYGHAVLRRPDPRFLHLYDFGNKYLr--dNEMIRLLHQMTDVIPRRLRTFKNISSPYPNVDCHSG 407
                        410       420       430       440       450
                 ....*....|....*....|....*....|....*....|....*....|.
Feature 1                         #   #                #  #         
4CTS_A       380 VLLQYYGMTEMNYYTVLFGVSRALGVLAQLIWSRALGFPLERPKSMSTDGL 430
6CSC_A       380 VLLQYYGMTEMNYYTVLFGVSRALGVLAQLIWSRALGFPLERPKSMSTAGL 430
gi 116475    406 VLLYSLGLTEYQYYTVVFAVSRALGCMANLIWSRAFGLPIERPGSADLKWF 456
gi 21356863  408 VLLQHYCLKELKFYTVLFGVSRALGVLSQLIWSRALGAPIERPKSFSSIEI 458
gi 45544838  380 VIQWYYGLREWDFYTVLFGVGRALGCMANITWDRGLGYAIERPKSVTTPML 430
gi 50551811  404 VLFHHYGIHETLYYTVTFGVSRALGPLPQLVWDRILGLPIERPKSLSLEEI 454
gi 71748976  427 VLLQHYGMKEQLFYTVLFGLSRQLGVLTGIVWDRLQGRPIERPKTMTSESL 477
gi 75034916  411 VLLQHYGLTEQNYYTVLFGLSRQMGVLAGVVWDRLQGRPLERPKSITTEML 461
gi 84994654  614 VLLSHFNVDQPQIFTVLFGLSRSMGILSQLVWARALRYPIERPKSLSLETV 664
gi 118376514 408 ALLYQLGIQEYQFYTVLFAISRSIGCLTNLVWCRAFGLPIERPESADLAYY 458

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