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


Conserved Protein Domain Family
citrate_synt

?
cd06101: citrate_synt 
Click on image for an interactive view with Cn3D
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 form 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. This subgroup includes both gram-positive and gram-negative bacteria.
Statistics
?
PSSM-Id: 99855
View PSSM: cd06101
Aligned: 21 rows
Threshold Bit Score: 263.79
Threshold Setting Gi: 13473292
Created: 6-Mar-2002
Updated: 17-Jan-2013
Structure
?
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: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
  • 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.
  • 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:1AJ8_A, Pyrococcus furiosus CS dimer bound with coenzyme A, contacts at 3.5 A.
    View structure with Cn3D
  • Citation:PMID 9254593
  • Structure:2C6X_A, Bacillus subtilis CS-I dimer bound with citrate, contacts at 3.5A
    View structure with Cn3D

Sequence Alignment
?
Format: Row Display: Color Bits: Type Selection:
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1          #                                                                            
4CTS_A       43 GGMRGMK-----GLVYETsVLDPde----------gIRFRGYSIPECqkmlpkakggeeplPEGLFWLLVTGQIPteeqv 107
1AMZ_A       41 GGMRGMK-----GLIYETsVLDPde----------gIRFRGFSIPECqkllpkagggeeplPEGLFWLLVTGQIPtpeqv 105
1CSH_A       41 GGMRGMK-----GLIYETsVLDPde----------gIRFRGFSIPECqkllpkagggeeplPEGLFWLLVTGQIPtpeqv 105
2C6X_A        3 YGLKGIT-----CVETSIsHIDGek---------grLIYRGHHAKDIaln---------hsFEEAAYLILFGKLPsteel 59
2CTS_A       43 GGMRGMK-----GLVYETsVLDPde----------gIRFRGYSIPECqkmlpkakggeeplPEGLFWLLVTGQIPteeqv 107
2IFC_A        9 KGLEDVN-----IKWTRLtTIDGnk---------giLRYGGYSVEDIias--------gaqDEEIQYLFLYGNLPteqel 66
6CSC_A       43 GGMRGMK-----GLIYETsVLDPde----------gIRFRGFSIPECqkllpkagggeeplPEGLFWLLVTGQIPtpeqv 107
6CTS_A       43 GGMRGMK-----GLVYETsVLDPde----------gIRFRGFSIPECqkllpkggxggeplPEGLFWLLVTGQIPtgaqv 107
gi 6456029   28 KGLRDINgkgvlAGLTNIsAIHSfdkegn--qipgvLEYRAYNIKDIvsdlrs---knrfgFEEMTYLLLFGELPsakel 102
gi 13473292  58 RGRSPSA-----IAESAIaWGEPsiataistvwhghLIYRGRDAAVLsdn---------atLEETAAVLWGLPEPirfea 123
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                       
4CTS_A      108 swlskewakraalpshvvtmldnfptnlhpmsqlsaaitalnsesnfarayaegihrtkyweliyedcmdliaklpcvaa 187
1AMZ_A      106 swvskewakraalpshvvtmldnfptnlhpmsqlsaaitalnsesnfarayaeginrtkywefvyedamdliaklpcvaa 185
1CSH_A      106 swvskewakraalpshvvtmldnfptnlhpmsqlsaaitalnsesnfarayaeginrtkywefvyedamdliaklpcvaa 185
2C6X_A       60 qvfkdklaaernlpehierliqslpnnmddmsvlrtvvsa---------------lgentytfhpkteeairliaitpsi 124
2CTS_A      108 swlskewakraalpshvvtmldnfptnlhpmsqlsaaitalnsesnfarayaegihrtkyweliyedcmdliaklpcvaa 187
2IFC_A       67 rkyketvqkgykipdfvinairqlpresdavamqmaavaama-----------asetkfkwnkdtdrdvaaemigrmsai 135
6CSC_A      108 swvskewakraalpshvvtmldnfptnlhpmsqlsaaitalnsesnfarayaeginrtkywefvyedamdliaklpcvaa 187
6CTS_A      108 swlskewakraalpshvvtmldnfptnlhpmsqlsaaitalnsesnfarayaegilrtkywemvyesamdliaklpcvaa 187
gi 6456029  103 qefqillaskrtlpeffvretiltnpssdvmnsmsrcllalasydk----kasdisienvleqslaliadfpllaiysyq 178
gi 13473292 124 papdaprqpgrasafaqlallagqar-------------------------------------------pslgrsaaslc 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                            #   #                      
4CTS_A      188 kiyrnlyregssigaidsklDWSHNFTNMlgy---tdaQFTELMRLYLTIHSDHEggNVSAHTSHLVGSALSDPYLSFAA 264
1AMZ_A      186 kiyrnlyragssigaidsklDWSHNFTNMlgy---tdpQFTELMRLYLTIHSDHEggNVSAHTSHLVGSALSDPYLSFAA 262
1CSH_A      186 kiyrnlyragssigaidsklDWSHNFTNMlgy---tdpQFTELMRLYLTIHSDHEggNVSAHTSHLVGSALSDPYLSFAA 262
2C6X_A      125 iayrkrwtrgeqaiapssqyGHVENYYYMltge-qpseAKKKALETYMILATEHGm-NASTFSARVTLSTESDLVSAVTA 202
2CTS_A      188 kiyrnlyregssigaidsklDWSHNFTNMlgy---tdaQFTELMRLYLTIHSDHEggNVSAHTSHLVGSALSDPYLSFAA 264
2IFC_A      136 tvnvyrhimnmpaelpkpsdSYAESFLNAafgr-katkEEIDAMNTALILYTDHEv-PASTTAGLVAVSTLSDMYSGITA 213
6CSC_A      188 kiyrnlyragssigaidsklDWSHNFTNMlgy---tdpQFTELMRLYLTIHSDHEggNVSAHTSHLVGSALSDPYLSFAA 264
6CTS_A      188 kiyrnlyragssigaidsklDWSHNFTNMlgy---tdaQFTELMRLYLTIHSDHEggNVSAHTSHLVGSALSDPYLSFAA 264
gi 6456029  179 ayihyfkkeslyihfpdpelTTAENILRMlrpdchysdMEAKVLDIALILHMEHGggNNSTFTTHVVTSSGTDTYATIAA 258
gi 13473292 161 adaaraigvlagalgaeagpDPVHRRLARgws---vddAGADAIRRALVLLADHEl-NASTFAARVAASTGASPAACLLA 236
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1              #### #  #                                      ########  #    #          
4CTS_A      265 AMNGLAGPLHGLANQEVLVWLTQLqkevgkd----vsdeklRDYIWNTLns-grVVPGYGHAVLRKTDPRYTCQREFALK 339
1AMZ_A      263 AMNGLAGPLHGLANQEVLLWLSQLqkdlgad----asdeklRDYIWNTLns-grVVPGYGHAVLRKTDPRYTCQREFALK 337
1CSH_A      263 AMNGLAGPLHGLANQEVLLWLSQLqkdlgad----asdeklRDYIWNTLns-grVVPGYGHAVLRKTDPRYTCQREFALK 337
2C6X_A      203 ALGTMKGPLHGGAPSAVTKMLEDIgek-----------ehaEAYLKEKLek-geRLMGFGHRVYKTKDPRAEALRQKAEE 270
2CTS_A      265 AMNGLAGPLHGLANQEVLVWLTQLqkevgkd----vsdeklRDYIWNTLns-grVVPGYGHAVLRKTDPRYTCQREFALK 339
2IFC_A      214 ALAALKGPLHGGAAEAAIAQFDEIkdp-----------amvEKWFNDNIingkkRLMGFGHRVYKTYDPRAKIFKGIAEK 282
6CSC_A      265 AMNGLAGPLHGLANQEVLLWLSQLqkdlgad----asdeklRDYIWNTLns-grVVPGYGHAVLRKTDPRYTCQREFALK 339
6CTS_A      265 AMNGLAGPLHGLANQEVLGWLAQLqkaxxxa----gadaslRDYIWNTLns-grVVPGYGHAVLRKTDPRYTCQREFALK 339
gi 6456029  259 ALSSLKGPKHGGANIKAAKMLENIkenisdynndeeikkylHQILNKEVfdkqgLIYGIGHAIYSVSDPRFEVFKSYVES 338
gi 13473292 237 GLATLSGPRHGGAGEAVMQLAEDAarh------------gaDAAIRRWLgh-drPLPAFGHPLYPDGDPRTTALSAAIPV 303
                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                          #  # #                      #   #            
4CTS_A      340 hlph----dpmFKLVAQLYKIVPNVlleqg-kaknPWPNVDAHSGVLLQYYGmte-mnYYTVLFGVSRALGVLAQLIWSR 413
1AMZ_A      338 hlps----dpmFKLVAQLYKIVPNVlleqg-kaknPWPNVDAHSGVLLQYYGmte-mnYYTVLFGVSRALGVLAQLIWSR 411
1CSH_A      338 hlps----dpmFKLVAQLYKIVPNVlleqg-kaknPWPNVDAHSGVLLQYYGmte-mnYYTVLFGVSRALGVLAQLIWSR 411
2C6X_A      271 vagndrdldlaLHVEAEAIRLLEIYkpg-----rkLYTNVEFYAAAVMRAIDfd--deLFTPTFSASRMVGWCAHVLEQA 343
2CTS_A      340 hlph----dpmFKLVAQLYKIVPNVlleqg-kaknPWPNVDAHSGVLLQYYGmte-mnYYTVLFGVSRALGVLAQLIWSR 413
2IFC_A      283 lsskkpevhkvYEIATKLEDFGIKAfgs-----kgIYPNTDYFSGIVYMSIGfplrnnIYTALFALSRVTGWQAHFIEYV 357
6CSC_A      340 hlps----dpmFKLVAQLYKIVPNVlleqg-kaknPWPNVDAHSGVLLQYYGmte-mnYYTVLFGVSRALGVLAQLIWSR 413
6CTS_A      340 hlpg----dpmFKLVAQLYKIVPNVlleqg-aaanPWPNVDAHSGVLLQYYGmte-mnYYTVLFGVSRALGVLAQLIWSR 413
gi 6456029  339 lakek-gleeeFKLYEKVAFLAPKVisenrkiyktICPNVDFYSGFVYKILEip--qeLFTPLFAIARIVGWLAHRMEEL 415
gi 13473292 304 -----------DETLQQLEKAAIAMt--------gARPNIDFALAALTRGLGlp--rdAPFQLFALGRSVGWAAHMVEQI 362
                       410
                ....*....|...
Feature 1           #  #     
4CTS_A      414 ALgfPLERPKSMS 426
1AMZ_A      412 ALgfPLERPKSMS 424
1CSH_A      412 ALgfPLERPKSMS 424
2C6X_A      344 ENn-MIFRPSAQY 355
2CTS_A      414 ALgfPLERPKSMS 426
2IFC_A      358 EEqqRLIRPRAVY 370
6CSC_A      414 ALgfPLERPKSMS 426
6CTS_A      414 ALgfPLERPKSMS 426
gi 6456029  416 INmnKIIRPAYES 428
gi 13473292 363 VSg-SIIRPRGRY 374

| Disclaimer | Privacy statement | Accessibility |
NCBI Home NCBI Search NCBI SiteMap