Conserved Protein Domain Family
CS_ACL-C_CCL

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cd06099: CS_ACL-C_CCL 
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Citrate synthase (CS), citryl-CoA lyase (CCL), the C-terminal portion of the single-subunit type ATP-citrate lyase (ACL) and the C-terminal portion of the large subunit of the two-subunit type ACL. CS catalyzes the condensation of acetyl coenzyme A (AcCoA) and oxalacetate (OAA) from 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. Some CS proteins function 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. CCL cleaves citryl-CoA (CiCoA) to AcCoA and OAA. ACLs catalyze an ATP- and a CoA- dependant cleavage of citrate to form AcCoA and OAA; they do this in a multistep reaction, the final step of which is likely to involve the cleavage of CiCoA to generate AcCoA and OAA. 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 CiCoA, and c) the hydrolysis of CiCoA to produce citrate and CoA. 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. 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. In fungi, yeast, plants, and animals ACL is cytosolic and generates AcCoA for lipogenesis. In several groups of autotrophic prokaryotes and archaea, ACL carries out the citrate-cleavage reaction of the reductive tricarboxylic acid (rTCA) cycle. In the family Aquificaceae this latter reaction in the rTCA cycle is carried out via a two enzyme system the second enzyme of which is CCL.
Statistics
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PSSM-Id: 99853
View PSSM: cd06099
Aligned: 19 rows
Threshold Bit Score: 229.917
Threshold Setting Gi: 13473292
Created: 6-Mar-2002
Updated: 17-Jan-2013
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 3 residues -Click on image for an interactive view with Cn3D
Feature 1:catalytic triad [active site]
Evidence:

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      208 DWSHNFTNMlgy---tdaQFTELMRLYLTIHSDHEggNVSAHTSHLVGSALSDPYLSFAAAMNGLaGPLHGLAnQEVLVW 284
1AMZ_A      206 DWSHNFTNMlgy---tdpQFTELMRLYLTIHSDHEggNVSAHTSHLVGSALSDPYLSFAAAMNGLaGPLHGLAnQEVLLW 282
1IXE_A      152 SHAANFLYMangv-epspEQARLMDAALILHAEHGf-NASTFTAIAAFSTETDLYSAITAAVASLkGPRHGGAnEAVMRM 229
2C6X_A      145 GHVENYYYMltge-qpseAKKKALETYMILATEHGm-NASTFSARVTLSTESDLVSAVTAALGTMkGPLHGGApSAVTKM 222
2CTS_A      208 DWSHNFTNMlgy---tdaQFTELMRLYLTIHSDHEggNVSAHTSHLVGSALSDPYLSFAAAMNGLaGPLHGLAnQEVLVW 284
6CTS_A      208 DWSHNFTNMlgy---tdaQFTELMRLYLTIHSDHEggNVSAHTSHLVGSALSDPYLSFAAAMNGLaGPLHGLAnQEVLGW 284
gi 6456029  199 TTAENILRMlrpdchysdMEAKVLDIALILHMEHGggNNSTFTTHVVTSSGTDTYATIAAALSSLkGPKHGGAnIKAAKM 278
gi 13473292 181 DPVHRRLARgws---vddAGADAIRRALVLLADHEl-NASTFAARVAASTGASPAACLLAGLATLsGPRHGGAgEAVMQL 256
gi 50551811 229 DWSYNYAAMmgkg--detGFVDLLRLYFALHGDHEggNVSAHATHLVGSALSDPYLSYSAGLQGLaGPLHGLAaQEVLRF 306
gi 56381113 151 SFAANFLYMltgk-epddIATEAFNKALVLHADHEl-NASTFTARVCVATLSDIYSGITAAIGALkGPLHGGAnEAVMKM 228
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                               #                                       
4CTS_A      285 LTQLqkevgkd----vsdeklRDYIWNTLns-grVVPGYGHAVLrKTDPRYTCQREFALKhlphd----pmfklVAQLYK 355
1AMZ_A      283 LSQLqkdlgad----asdeklRDYIWNTLns-grVVPGYGHAVLrKTDPRYTCQREFALKhlpsd----pmfklVAQLYK 353
1IXE_A      230 IQEIgtp-----------eraREWVREKLak-keRIMGMGHRVYkAFDPRAGVLEKLARLvaekhgh-skeyqiLKIVEE 296
2C6X_A      223 LEDIgek-----------ehaEAYLKEKLek-geRLMGFGHRVYkTKDPRAEALRQKAEEvagndrdldlalhvEAEAIR 290
2CTS_A      285 LTQLqkevgkd----vsdeklRDYIWNTLns-grVVPGYGHAVLrKTDPRYTCQREFALKhlphd----pmfklVAQLYK 355
6CTS_A      285 LAQLqkaxxxa----gadaslRDYIWNTLns-grVVPGYGHAVLrKTDPRYTCQREFALKhlpgd----pmfklVAQLYK 355
gi 6456029  279 LENIkenisdynndeeikkylHQILNKEVfdkqgLIYGIGHAIYsVSDPRFEVFKSYVESlakekgl-eeefklYEKVAF 357
gi 13473292 257 AEDAarh------------gaDAAIRRWLgh-drPLPAFGHPLYpDGDPRTTALSAAIPVde-----------tLQQLEK 312
gi 50551811 307 ILDMeknvpkg----ysnedlVKYLWSVLks-grVIPGYGHAVLrKPDPRFEALMNFANSrqeird--dpvfqlVSRTSE 379
gi 56381113 229 LTEIgtv-----------dnvEPYIRRKLan-keKIMGFGHRVYrKGDPRAKHLKKMSEKltklvge-phwyemSTKIEE 295
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
Feature 1                           #                                                   
4CTS_A      356 IVPNVlleqg-kaknPWPNVDAHSGVLLQYYgmtemnYYTVLFGVSRALGVLAQLIWSRALgfPLERPKSMS 426
1AMZ_A      354 IVPNVlleqg-kaknPWPNVDAHSGVLLQYYgmtemnYYTVLFGVSRALGVLAQLIWSRALgfPLERPKSMS 424
1IXE_A      297 EAGKVlnp-----rgIYPNVDFYSGVVYSDLgfs-leFFTPIFAVARISGWVGHILEYQELdnRLLRPGAKY 362
2C6X_A      291 LLEIYkpg-----rkLYTNVEFYAAAVMRAIdfd-deLFTPTFSASRMVGWCAHVLEQAENn-MIFRPSAQY 355
2CTS_A      356 IVPNVlleqg-kaknPWPNVDAHSGVLLQYYgmtemnYYTVLFGVSRALGVLAQLIWSRALgfPLERPKSMS 426
6CTS_A      356 IVPNVlleqg-aaanPWPNVDAHSGVLLQYYgmtemnYYTVLFGVSRALGVLAQLIWSRALgfPLERPKSMS 426
gi 6456029  358 LAPKVisenrkiyktICPNVDFYSGFVYKILeip-qeLFTPLFAIARIVGWLAHRMEELINmnKIIRPAYES 428
gi 13473292 313 AAIAMt--------gARPNIDFALAALTRGLglp-rdAPFQLFALGRSVGWAAHMVEQIVSg-SIIRPRGRY 374
gi 50551811 380 VATGVltehg-ktknPHPNVDSSSGVLFHHYgihetlYYTVTFGVSRALGPLPQLVWDRILglPIERPKSLS 450
gi 56381113 296 IVTSEk--------aLPPNVDFYSASVYHCLgid-hdLFTPIFAVSRTSGWLAHILEQYDNn-RLIRPRAEY 357

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