3EWB,3EEG


Conserved Protein Domain Family
DRE_TIM_IPMS

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cd07940: DRE_TIM_IPMS 
Click on image for an interactive view with Cn3D
2-isopropylmalate synthase (IPMS), N-terminal catalytic TIM barrel domain
2-isopropylmalate synthase (IPMS) catalyzes an aldol-type condensation of acetyl-CoA and 2-oxoisovalerate yielding 2-isopropylmalate and CoA, the first committed step in leucine biosynthesis. This family includes the Arabidopsis thaliana IPMS1 and IPMS2 proteins, the Glycine max GmN56 protein, and the Brassica insularis BatIMS protein. This family also includes a group of archeal IPMS-like proteins represented by the Methanocaldococcus jannaschii AksA protein. AksA catalyzes the condensation of alpha-ketoglutarate and acetyl-CoA to form trans-homoaconitate, one of 13 steps in the conversion of alpha-ketoglutarate and acetylCoA to alpha-ketosuberate, a precursor to coenzyme B and biotin. AksA also catalyzes the condensation of alpha-ketoadipate or alpha-ketopimelate with acetylCoA to form, respectively, the (R)-homocitrate homologs (R)-2-hydroxy-1,2,5-pentanetricarboxylic acid and (R)-2-hydroxy-1,2,6- hexanetricarboxylic acid. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".
Statistics
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PSSM-Id: 163678
View PSSM: cd07940
Aligned: 121 rows
Threshold Bit Score: 340.195
Threshold Setting Gi: 257168417
Created: 22-Sep-2009
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 12 residues -Click on image for an interactive view with Cn3D
Feature 1:active site [active site]
Evidence:
  • Comment:Based on the active site of the Mycobacterium tuberculosis LeuA isopropylmalate synthase.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1             ##  #                          #                              #           
3EWB_X        8 FFDTTLRDGEQTPGVNFDVKEKIQIALQLEKLGIDVIEAGFPISSPGDFECVKAIAKaikhcSVTGLARCVEGDIDRAEE 87  Listeria monocyt...
YP_931306    32 IFDTTLRDGEQMPGVALSNEEKLQIALALDEAGVDMIEAGFAAVSKDEQIAIRQIAKevyraDVVSLARMSKSDVDAAVS 111 Pyrobaculum isla...
YP_023691    31 IFDTTLRDGEQSPGVSFNINQKARIAGMLVDLGVDMIETGFAAVSSEESMAIRKIHEmd--gNFISLARCNRHDIDSVID 108 Picrophilus torr...
NP_275866     5 VLDTTLRDGEQTPGVSLTPEEKLRIALKIDALGADIIEAGSAITSEGEREGIRKITSeglraEICSFARAVREDIDAAIS 84  Methanothermobac...
YP_448338     7 ILDTTLRDGEQTPGVLITSNEKLRIASKLDELGVDVIEAGSAITSKDEQKSIKTITEnklnaEICSFARPMKIDIDTALD 86  Methanosphaera s...
Q58787        5 IFDTTLRDGEQTPGVSLTPNDKLEIAKKLDELGVDVIEAGSAITSKGEREGIKLITKeglnaEICSFVRALPVDIDAALE 84  Methanocaldococc...
ZP_03705283   5 ILDTTLRDGEQTPGVSLTSLEKLRIATKLDEIGVNFIEAGSAITSEGERQSIKDITQqnfnaEILSFSRPLEMDIDYCLE 84  Methanobrevibact...
AAU83699      9 ILDTTLRDGEQTPGVSLTPEQKLQIAKQLDILGVDFIEAGTAIISEGEQKAIKAIAAeglkaEISSFARLLKGDIDAAIK 88  uncultured archa...
ACV46176     24 FLDTTLRDGEQAPGISLSPDEKARIARQLDAAEIDVIEAGSACTGPGERKTISRVADldldaTVTSFCRGIRNDIDLALE 103 Halomicrobium mu...
NP_248395     5 IFDTTLRDGEQTPGVSLTPNDKLEIAKKLDELGVDVIEAGSAITSKGEREGIKLITKeglnaEICSFVRALPVDIDAALE 84  Methanocaldococc...
Feature 1                 #                                         # #                         
3EWB_X       88 alkdavspQIHIFLATSDVHXEYKlkxsraevLASIKHHISYARQKfdVVQFSPEDATRSDRAFLIEAVQTAIdagatVI 167 Listeria monocyt...
YP_931306   112 ad----vdMVHVFIATSDIHLKYKlgisreeaLRRVEEVVSYAKSYgvKVLFSAEDATRSDLEFLARVYKTAIeagadEI 187 Pyrobaculum isla...
YP_023691   109 tg----idNIHLFIATSDIHIKYKlktsreniMEKIVDSIDYARSHglNVLFSPEDATRTDMNFLIDVINTAIssgayEI 184 Picrophilus torr...
NP_275866    85 cd----vdSVHLVVPTSDLHLEHKlrktreevLEQAVDCTEYAVDHgiLVELSAEDSTRSDMDFLRTIFREGIeagaeRI 160 Methanothermobac...
YP_448338    87 cd----vdSIHLVIPSSDLHIDYKlrktreqvEEMAVNATEYAKSHglIVELSTEDATRTGMDDLKHLYNQCIevgadRL 162 Methanosphaera s...
Q58787       85 cd----vdSVHLVVPTSPIHMKYKlrktedevLETALKAVEYAKEHglIVELSAEDATRSDVNFLIKLFNEGEkvgadRV 160 Methanocaldococc...
ZP_03705283  85 cd----vdAVNLVVPTSDLHIFDKlkitkeelLAMSNSAVDYCKDHglTVELSAEDASRTSIDFLKTVYVNAIehgadRV 160 Methanobrevibact...
AAU83699     89 cg----vdTVNLVAPVSDDHIKKKlrkdretlRDMTIEMSEYVKGHglKVEISAEDASRADMGFLKSFFYDLGqi-vdRL 163 uncultured archa...
ACV46176    104 cg----vdGINLVVPASDRHVEDKvgtsrednVASTVELVEYAKAQglWVEVIGEDGSRADLDYLEELLGAAIdagadRI 179 Halomicrobium mu...
NP_248395    85 cd----vdSVHLVVPTSPIHMKYKlrktedevLETALKAVEYAKEHglIVELSAEDATRSDVNFLIKLFNEGEkvgadRV 160 Methanocaldococc...
Feature 1         # #                              # #                                          
3EWB_X      168 NIPDTVGYTNPTEFGQLFQDLRREikqfddiiFASHCHDDLGXATANALAAIENGARRVEGTINGIGERAGNTALEEVAV 247 Listeria monocyt...
YP_931306   188 NVPDTVGIMTPSRMAYLIRFLRERlpp---vpMHIHCHDDFGMAVANTITAIENGADVAQVVVNNFGERAGNAALEEVVA 264 Pyrobaculum isla...
YP_023691   185 NIPDTIGIMNPISMYNFIHEIKNRtk----scISVHCHNDFGMATANTLAAIMAGADGAQVTVNGIGERAGNAALEEVVL 260 Picrophilus torr...
NP_275866   161 CACDTVGILTPERSYEFYRGLSELga-----pLSVHCHNDFGLAVANSLAGLRAGASEVHATINGIGERAGNAALEEVVV 235 Methanothermobac...
YP_448338   163 CACDTVGILTPERSYEFYKELAQLpq-----pLSVHCHNDFGLAVANTLAALNAGAQQAHVTINGLGERAGNASCEELVM 237 Methanosphaera s...
Q58787      161 CVCDTVGVLTPQKSQELFKKITENvn----lpVSVHCHNDFGMATANTCSAVLGGAVQCHVTVNGIGERAGNASLEEVVA 236 Methanocaldococc...
ZP_03705283 161 CLCDTVGILTPESSFEMFKQLKEDid----vpISCHCHNDFGLAVANTFAALKGGASEFHSTINGIGERAGNTSFEECVV 236 Methanobrevibact...
AAU83699    164 SFCDTVGVLYPERTKEMFQALCSCdt-----pVSVHCHNDFGLATANSVAAVMAGAKVVHVTVNGLGERAGNASLDEVVT 238 uncultured archa...
ACV46176    180 CWADTVGHATPDGALEAVSRLSKLg------pVSAHTHDDLGLAVMNALVAVAAGADMVHGTINGIGERAGNVALEEVAI 253 Halomicrobium mu...
NP_248395   161 CVCDTVGVLTPQKSQELFKKITENvn----lpVSVHCHNDFGMATANTCSAVLGGAVQCHVTVNGIGERAGNASLEEVVA 236 Methanocaldococc...
Feature 1                                    
3EWB_X      248 ALHirkdfyqaeTNIVLNQFKNSSDLISR 276 Listeria monocytogenes str. 4b F2365
YP_931306   265 ALHfll---gmrTNVKLEKLYELSQLVSK 290 Pyrobaculum islandicum DSM 4184
YP_023691   261 SVHaft---dcsTGINMRMIPKISKYVSM 286 Picrophilus torridus DSM 9790
NP_275866   236 ALKsly---dvdTSINIEMLYETSRMVAR 261 Methanothermobacter thermautotrophicus str. Delta H
YP_448338   238 AIEsly---nikTGIKTELFYEISQLVER 263 Methanosphaera stadtmanae DSM 3091
Q58787      237 ALKily---gydTKIKMEKLYEVSRIVSR 262 Methanocaldococcus jannaschii
ZP_03705283 237 GIYklfp--qfsTDIKIHEIYTISKLVAR 263 Methanobrevibacter smithii DSM 2374
AAU83699    239 ALElly---gvkTNIAKEKMYETSRVVMN 264 uncultured archaeon GZfos32G12
ACV46176    254 ALDhgy----gvETMDLTEVYDLAQLVAN 278 Halomicrobium mukohataei DSM 12286
NP_248395   237 ALKily---gydTKIKMEKLYEVSRIVSR 262 Methanocaldococcus jannaschii DSM 2661

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