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


Conserved Protein Domain Family
ScCit1-2_like

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cd06105: ScCit1-2_like 
Click on image for an interactive view with Cn3D
Saccharomyces cerevisiae (Sc) citrate synthases Cit1-2_like. Citrate synthases (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). ScCit1 is a nuclear-encoded mitochondrial CS with highly specificity for AcCoA. In addition to its CS function, ScCit1 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. Chicken and pig heart CS, two Arabidopsis thaliana (Ath) CSs, CSY4 and -5, and Aspergillus niger (An) CS also belong to this group. Ath CSY4 has a mitochondrial targeting sequence; AthCSY5 has no identifiable targeting sequence. AnCS encoded by the citA gene has both an N-terminal mitochondrial import signal and a C-terminal peroxisiomal target sequence; it is not known if both these signals are functional in vivo. 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: 99858
View PSSM: cd06105
Aligned: 24 rows
Threshold Bit Score: 857.821
Threshold Setting Gi: 158270890
Created: 24-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
461745          45 LKERFAEIIPAKAEEIKKFKKEHGKTVIGEVLLEQAYGGMRGIKGLVWEGSVLDPEEGIRFRGRTIPEIQReLPKAEGST 124 baker's yeast
Q10306          42 LKDRLAELIPEKQAEIKKFRAEHGQDVIGEVTINQMYGGARGVRSLIWEGSVLDPNEGIRFRGYTIPECQKlLPSSPNGK 121 Schizosacchar...
TIGR:At2g44350  40 LKSQLQELIPEQQDRLKKLKSEHGKVQLGNITVDMVIGGMRGMTGLLWETSLLDPEEGIRFRGLSIPECQKvLPTAQSGA 119 thale cress
P34085          38 LKERFAELLPENIEKIKALRKEHGSKVVDKVTLDQVYGGARGIKCLVWEGSVLDAEEGIRFRGKTIPECQElLPKAPGGK 117 Neurospora cr...
P20115          41 LKSQLQELIPEQQDRLKKLKSEHGKVQLGNITVDMVIGGMRGMTGLLWETSLLDPEEGIRFRGLSIPECQKvLPTAQSGA 120 thale cress
BAF31127        14 LKERLAELIPVELEHVKAVRAEHGKKAFGPVVVDQLYGGMRGLPALIWEGSVLDPEEGIRFRGKSIPECQElLPKAPGGN 93  Phanerochaete...
CAL53932         4 LKARVREAIPETNARLKAIRAAHGEKRVGEVTVGMVMGGMRGITGMLYETSLLDAEEGIRFRGHTIPDLQRrLPKATANG 83  Ostreococcus ...
CAO67184        40 LHSQLKELIPEQQERLKKLKAECGKIQLGNITVDMVLGGMRGMTGLLWETSLLDPDEGIRFRGMSIPECQKvLPNATPGG 119 Vitis vinifera
Feature 1                                                                                          
4CTS_A          86 EPLPEGLFWLLVTGQIPTEEQVSWLSKEWAKRAALPSHVVTMLDNFPTNLHPMSQLSAAITALNSESNFARAYAEGIHRT 165 pig
6CSC_A          86 EPLPEGLFWLLVTGQIPTPEQVSWVSKEWAKRAALPSHVVTMLDNFPTNLHPMSQLSAAITALNSESNFARAYAEGINRT 165 chicken
461745         125 EPLPEALFWLLLTGEIPTDAQVKALSADLAARSEIPEHVIQLLDSLPKDLHPMAQFSIAVTALESESKFAKAYAQGVSKK 204 baker's yeast
Q10306         122 QPLPESLFWLLVTGEIPTLSQVQALSADWAARSQLPKFVEELIDRCPPTLHPMAQFSLAVTALEHDSAFAKAYERGMNKH 201 Schizosacchar...
TIGR:At2g44350 120 EPLPEGLLWLLLTGKVPSKEQVEALSKDLANRAAVPDYVYNAIDALPSTAHPMTQFASGVMALQVQSEFQKAYENGIHKS 199 thale cress
P34085         118 EPLPEGLFWLLLTGEVPSEQQVRDLSAEWAARSDVPKFIEELIDRCPSDLHPMAQLSLAVTALEHTSSFARAYAKGINKK 197 Neurospora cr...
P20115         121 EPLPEGLLWLLLTGKVPSKEQVEALSKDLANRAAVPDYVYNAIDALPSTAHPMTQFASGVMALQVQSEFQKAYENGIHKS 200 thale cress
BAF31127        94 EPLPEALFWLLVTGEVPTQEQVTALSKDWAARAAIPEFVEELLDRCPPTLHPMSQFSLAVTALNHDSNFAKAYQQGISKK 173 Phanerochaete...
CAL53932        84 EPLPEGIMWLMLTGEIPSDAEVKTLSQELAARAELPKAVHDVLDALPKNTHPMTQLSCALMAMQPESKFAKAYQDGVHKT 163 Ostreococcus ...
CAO67184       120 EPLPEGLLWLLLTGKVPTKGQVDALSKELSTRATVPDHVYKAIDALPQSAHPMTQFATGVMALQVQSEFQKAYEKGIPKS 199 Vitis vinifera
Feature 1                                                                                   #   #  
4CTS_A         166 KYWELIYEDCMDLIAKLPCVAAKIYRNLYReGSSIGAIDSkLDWSHNFTNMLGYtd-aQFTELMRLYLTIHSDHEGGNVS 244 pig
6CSC_A         166 KYWEFVYEDAMDLIAKLPCVAAKIYRNLYRaGSSIGAIDSkLDWSHNFTNMLGYtd-pQFTELMRLYLTIHSDHEGGNVS 244 chicken
461745         205 EYWSYTFEDSLDLLGKLPVIASKIYRNVFK-DGKITSTDPnADYGKNLAQLLGYen-kDFIDLMRLYLTIHSDHEGGNVS 282 baker's yeast
Q10306         202 DYWKYEYEDCMDLIAKTVPIAGRIYRNLYR-DGVVAPIQMdKDHSYNFANVLGFanneEFVELMRLYLTIHADHEGGNVS 280 Schizosacchar...
TIGR:At2g44350 200 KFWEPTYEDCLNLIARVPVVAAYVYRRMYK-NGDSIPSDKsLDYGANFSHMLGFdd-eKVKELMRLYITIHSDHEGGNVS 277 thale cress
P34085         198 EYWGYTFEDSMDLIAKLPTIAARIYQNVFK-GGKVAAVQKdKDYSFNFANQLGFgdnkDFVELLRLYLTIHTDHEGGNVS 276 Neurospora cr...
P20115         201 KFWEPTYEDCLNLIARVPVVAAYVYRRMYK-NGDSIPSDKsLDYGANFSHMLGFdd-eKVKELMRLYITIHSDHEGGNVS 278 thale cress
BAF31127       174 DYWGPVFEDCMDLIAKLPNIAGRIFRNVYG-KGKLPAIDAnKDYSWNLATLLGFgenpAFVELMRLYITIHSDHEGGNVS 252 Phanerochaete...
CAL53932       164 TFWEYAFEDSMDIIARLPAVCAAIYRRTFK-DGKLIAADKnLDWAGNFAHMMGHds-eAVKELMRLYMTIHVDHEGGNVS 241 Ostreococcus ...
CAO67184       200 KYWEPTYEDSLSLIAQVPVVAAYVYRRVYK-NGQIIPKDDsLDYGANFSHMLGFds-pKMQELMRLYVTIHSDHEGGNVS 277 Vitis vinifera
Feature 1                                     #### #  #                                 ########  #
4CTS_A         245 AHTSHLVGSALSDPYLSFAAAMNGLAGPLHGLANQEVLVWLTQLqkevGKDVSdekLRDYIWNTLNSGRVVPGYGHAVLR 324 pig
6CSC_A         245 AHTSHLVGSALSDPYLSFAAAMNGLAGPLHGLANQEVLLWLSQLqkdlGADASdekLRDYIWNTLNSGRVVPGYGHAVLR 324 chicken
461745         283 AHTTHLVGSALSSPYLSLAAGLNGLAGPLHGRANQEVLEWLFKLreevKGDYSketIEKYLWDTLNAGRVVPGYGHAVLR 362 baker's yeast
Q10306         281 AHTGHLVGSALSSPFLSMAASLNGLAGPLHGLANQEVLNFLITMkkeiGDDLSeetIKSYLWKLLNSGRVVPGYGHAVLR 360 Schizosacchar...
TIGR:At2g44350 278 AHTGHLVGSALSDPYLSFAAALNGLAGPLHGLANQEVLLWIKSVveecGEDISkeqLKEYVWKTLNSGKVIPGYGHGVLR 357 thale cress
P34085         277 AHTTHLVGSALSSPFLSVAAGLNGLAGPLHGLANQEVLNWLTEMkkviGDDLSdeaITKYLWDTLNAGRVVPGYGHAVLR 356 Neurospora cr...
P20115         279 AHTGHLVGSALSDPYLSFAAALNGLAGPLHGLANQEVLLWIKSVveecGEDISkeqLKEYVWKTLNSGKVIPGYGHGVLR 358 thale cress
BAF31127       253 AHTGKLVGSALSDPFLAFAASLNGLAGPLHGLANQEVLIWLRRMqskiGENASdeaVREYVWSTLKSGQVVPGYGHAVLR 332 Phanerochaete...
CAL53932       242 AHTTHLVGSALSDPYLSLVAGLNGLAGPLHGLANQEVLKWLNETrekvGDDATkeqLTEFVWDTLKSGRVVPGYGHGVLR 321 Ostreococcus ...
CAO67184       278 AHTGHLVASALADPYLSFAAALNGLAGPLHGLANQEVLLWIKSVvdecGENISteqLKDYVWKTLKSGKVVPGFGHGVLR 357 Vitis vinifera
Feature 1              #                                        #  # #                     #   #   
4CTS_A         325 KTDPRYTCQREFALKHLPHDPMFKLVAQLYKIVPNVLLEQGKAKNPWPNVDAHSGVLLQYYGMTEMNYYTVLFGVSRALG 404 pig
6CSC_A         325 KTDPRYTCQREFALKHLPSDPMFKLVAQLYKIVPNVLLEQGKAKNPWPNVDAHSGVLLQYYGMTEMNYYTVLFGVSRALG 404 chicken
461745         363 KTDPRYTAQREFALKHFPDYELFKLVSTIYEVAPGVLTKHGKTKNPWPNVDSHSGVLLQYYGLTEASFYTVLFGVARAIG 442 baker's yeast
Q10306         361 KTDPRYTAQREFALEHLPKDPMFQLVSRLYEIVPGVLTEHGKTKNPYPNVDSHSGVLLQYYGLKEQSFYTVLFGVSRTLG 440 Schizosacchar...
TIGR:At2g44350 358 NTDPRYVCQREFALKHLPDDPLFQLVSKLYEVVPPVLTELGKVKNPWPNVDAHSGVLLNHYGLTEARYYTVLFGVSRSLG 437 thale cress
P34085         357 KTDPRYSAQRKFAQEHLPEDPMFQLVSQVYKIAPKVLTEHGKTKNPYPNVDAHSGVLLQHYGLTEANYYTVLFGVSRAIG 436 Neurospora cr...
P20115         359 NTDPRYVCQREFALKHLPDDPLFQLVSKLYEVVPPVLTELGKVKNPWPNVDAHSGVLLNHYGLTEARYYTVLFGVSRSLG 438 thale cress
BAF31127       333 KTDPRYTAQREFALKHLPNDPMFKLVGQIYNIVPGILLEAGKAKNPWPNVDAHSGVLLTHYGLTQMNFYTVLFGVSRAFG 412 Phanerochaete...
CAL53932       322 KTDPRYTCQREFALKHLPNDPMFKLVGKLFEVVPDVLTQTGKVKNPWPNVDAHSGVLLQYYGITEENFYTVLFGASRAIG 401 Ostreococcus ...
CAO67184       358 KTDPRYMCQREFALKHLPDDPLFQLVSKLYEVVPPILTELGKVKNPWPNVDAHSGVLLNHFGLHEARYFTVLFGVSRSIG 437 Vitis vinifera
Feature 1                       #  #            
4CTS_A         405 VLAQLIWSRALGFPLERPKSMSTDGLIKL 433 pig
6CSC_A         405 VLAQLIWSRALGFPLERPKSMSTAGLEKL 433 chicken
461745         443 VLPQLIIDRAVGAPIERPKSFSTEKYKEL 471 baker's yeast
Q10306         441 VASQLIWDRALGLPIERPKSFSTEALKKM 469 Schizosaccharomyces pombe
TIGR:At2g44350 438 ICSQLIWDRALGLALERPKSVTMDWLEAH 466 thale cress
P34085         437 VLPQLIIDRAVGAPIERPKSYSTDKWIEI 465 Neurospora crassa
P20115         439 ICSQLIWDRALGLALERPKSVTMDWLEAH 467 thale cress
BAF31127       413 VAAQLIWDRALGAPLERPKSYSTGAIEKM 441 Phanerochaete chrysosporium
CAL53932       402 VLSQLILSRASGYPIERPKSVTSKWIEDK 430 Ostreococcus tauri
CAO67184       438 ICSQLIWDRALGLPLERPKSVTMEWLENH 466 Vitis vinifera

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