1SR9,3FIG


Conserved Protein Domain Family
DRE_TIM_LeuA

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cd07942: DRE_TIM_LeuA 
Click on image for an interactive view with Cn3D
Mycobacterium tuberculosis LeuA3 and related proteins, N-terminal catalytic TIM barrel domain
Alpha-isopropylmalate synthase (LeuA), a key enzyme in leucine biosynthesis, catalyzes the first committed step in the pathway, converting acetyl-CoA and alpha-ketoisovalerate to alpha-isopropyl malate and CoA. Although the reaction catalyzed by LeuA is similar to that of the Arabidopsis thaliana IPMS1 protein, the two fall into phylogenetically distinct families within the same superfamily. LeuA has and N-terminal TIM barrel catalytic domain, a helical linker domain, and a C-terminal regulatory domain. LeuA forms a homodimer in which the linker domain of one monomer sits over the catalytic domain of the other, inserting residues into the active site that may be important for catalysis. Homologs of LeuA are found in bacteria as well as fungi. This family includes alpha-isopropylmalate synthases I (LEU4) and II (LEU9) from Saccharomyces cerevisiae. 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: 163680
View PSSM: cd07942
Aligned: 40 rows
Threshold Bit Score: 481.3
Threshold Setting Gi: 150386044
Created: 14-Sep-2009
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 8 residues -Click on image for an interactive view with Cn3D
Feature 1:active site [active site]
Evidence:
  • Structure:1SR9_A; Mycobacterium tuberculosis LeuA binds Zn2+ and alpha-ketoisovalerate, contacts at 4A.
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                ##                             #                                       
1SR9_A       71 APLWCAVDLRDGNQALIDPXSPARKRRXFDLLVRXGYKEIEVGFPSASQTDFDFVREIIEqgaiPDDVTIQVLTQCRPEL 150 Mycobacterium tu...
ZP_01924626  28 PPAWVSVDLRDGNQAFARPMNVATKIRYFQMLTQIGFKEIEVAYPASSAEEFEFVRRLIAenliPDDVRISVLTAARENL 107 Victivallis vade...
ZP_01873876  25 SPTWCAVDLRDGNQALPDPLTLEQKKIYFDILVKIGFKEIEIGFPSASKDDYDFCRHLIDnkviPDDVMISVLVPARPDL 104 Lentisphaera ara...
ZP_01923827  39 PPVWASVDLRDGNQALPEPMGPEHKLEYFNMLVGIGFKEIEVAFPSASADDFNFVRMLIErnliPDDVRISVLTQARRHL 118 Victivallis vade...
YP_574561    30 APTWVSEDLRDGNQALLEPMSVEQKQRFWHQIIKVGIKEVMVGFPSASQPDYDFVRWLIEedqiPDDVTIAVLVQCREHL 109 Chromohalobacter...
ZP_02037985  44 APIWCSVDLRDGNQALVDPMNLQEKLEYFHTLVDIGVKEIEIGFPSASETEYEICRELIEgghiPDDVTIQVLVQARPHL 123 Bacteroides capi...
YP_392142    27 APIWASVDLRDGNQALANPMTVEQKLKLWDQLVAIGFKTIEIGFPAASQLEFDFARRLIEenriPDDVTVQVLVQAREHL 106 Thiomicrospira c...
Q8UD63       29 APIWCSVDLRDGNQSLVNPMGHDRKARMFKLLLEMGFKEIEIGFPSASQTDFDFARWCVEegnvPDDVSLQVLVQCRPEL 108 Agrobacterium tu...
ZP_03727786  30 APVWCSVDLRDGNQALAQPMSVEEKLEYFAMLVRIGFKEIEVGFPSASQIEFDFCRRLIDddliPDDVAIQVLCQCREEL 109 Opitutaceae bact...
ZP_02927930  30 APRWCSVDLRDGNQALAAPMNVSQKLEMFDALVRCGFKEIEVGFPSASNTEFAFNRRLIEdgriPDDVTVQVLVQAREDL 109 Verrucomicrobium...
Feature 1                                                                             #         
1SR9_A      151 IERTFQACSGapraIVHFYNSTSILQRRVVFRANRAE-VQAIATDGARKCVEQaakyp--gtqwRFEYSPESYTGTELEY 227 Mycobacterium tu...
ZP_01924626 108 IARTIESLQGvrqaTIHCYVATSDLHREFVFHKTEAE-ITEMAVSATKMIAEAleqng-mrdaiHYEFSPEEFSDSRLGF 185 Victivallis vade...
ZP_01873876 105 VVKTMDALRDvpkaTVHFYVATSDLHREHVLGKSHQE-VFEMCTATVQSIKEEasklk--estfYLEFSPEEFTDTDLDF 181 Lentisphaera ara...
ZP_01923827 119 IDRTIESLRGvkhaIAHCYVPTSDLHGRFVFNHNREE-VKQMAVDGTRMVKEAiereg-lwgkvAYEFSPEEFTDSDLDF 196 Victivallis vade...
YP_574561   110 IERTFESLVGakraIVHLYNSTSTVQRERVFEMDRAG-IVDIAVQGASWVKERaaryp--dvdwRFEYTPESFSSTEIDF 186 Chromohalobacter...
ZP_02037985 124 IQKTFEAIRGakhvILHFYNSTSTLQRKVVFHMDMDG-ITKIATDAAKLIYELsqpviaegmdlRYEYSPESFMGTEMDY 202 Bacteroides capi...
YP_392142   107 IKRTYEALQGvkqaVVHVYNTTSTVQREKVFCKSKAD-IKAMAIQGAKWVQSYakehp--esdwVFQYSPESFSQTETDY 183 Thiomicrospira c...
Q8UD63      109 ITRTFEALEGankpIIHFYNSTSELQRRVVFGKDVHG-IKQIAVDAAKMITDMaaka---gggfRFEYSPESFTGTELEV 184 Agrobacterium tu...
ZP_03727786 110 ITRSLEALRGakkiIFHLYNSTSPYQRKYVFGDASREeIKAIAVHGVQLLRKHaaplieegshiQLQYSPESFNSTELDF 189 Opitutaceae bact...
ZP_02927930 110 IEKTVQSLIGakkvIIHLYNSTSPAQRRYVFGMEKED-ILKMAVRGAQMIKERlprle--gadvSLQYSPESFSATEVEF 186 Verrucomicrobium...
Feature 1                                   # #                              # #                
1SR9_A      228 AKQVCDAVGEVIAPtpe----rpiIFNLPATVEXTTPNVYADSIEWXSRNlanresviLSLHPHNDRGTAVAAAELGFAA 303 Mycobacterium tu...
ZP_01924626 186 IVDLASAVHDAWRPngk----adfILNLPATVERRPPYEYADMVEAFTRSypymadttLSVHTHNDQGGAVAAAEMAVLA 261 Victivallis vade...
ZP_01873876 182 AVEVCDHVIEQWQPaad----ekvILNLPATVERRPPTHYADMIELFQRKlkse-qaiISLHAHNDMGCAVASTQLAIQA 256 Lentisphaera ara...
ZP_01923827 197 VVEVCCAVKEVWGPstp----dmlILNLPATVERRPPNQYADMIELFCRKfpylnevgLSLHAHNDQGCAVAATELALLA 272 Victivallis vade...
YP_574561   187 SLDICEAVMDVWQPtpd----nkcILNLPTTVEVAGPHHHADQIDYFCQHisrrdsviISVHTHNDRGGAVAAAELAMLA 262 Chromohalobacter...
ZP_02037985 203 AVEICQAVIEAIHAtpe----kkiILNLPTTVENCMPNYFADELEYFISKlpsrdsaiISLHPHNDRGCGVATAEMGLLA 278 Bacteroides capi...
YP_392142   184 AVEVCQAVMDVWQPtpd----nrcILNLPATVESTSPNRFADQVEYFITHlknresaiISIHTHNDRGCAVAAAELSLLA 259 Thiomicrospira c...
Q8UD63      185 ALEICNAVVEVVKPtad----nklILNLPSTVEMATPNIYADQIEWMCRNidnrenviISLHPHNDRGTGIAATELALMA 260 Agrobacterium tu...
ZP_03727786 190 SLEICEAVTDVWQPmldanpadkiILNLPATVEYTTPNIHADQIEWMSTHltrrdrtlLSLHTHNDRGTGVAATELALLA 269 Opitutaceae bact...
ZP_02927930 187 AKEISEAVIDVWQPtpe----rkmILNLPDTVEVAMPNVYADQIEWIATNirnreslvISLHTHNDRGTGTAATELGLLA 262 Verrucomicrobium...
Feature 1                                                          
1SR9_A      304 GADRIEGCLFGNGERTGNVCLVTLGLNLFSRGVDPQIDFSNIDEIRRTVEY 354 Mycobacterium tuberculosis
ZP_01924626 262 GAERVEGTLCGHGERTGNMDLVMFALNLKSRGVDPGLDFSNLPEIVEFIEE 312 Victivallis vadensis ATCC BAA-548
ZP_01873876 257 GAHRVEGTLFGQGERSGNVDLITLVLNLQYLGIDTGLDFSDLMNITEQISE 307 Lentisphaera araneosa HTCC2155
ZP_01923827 273 GATRVEGTVFGHGERTGNLDVSVLALNMESRGVRTGLNFSNMPEIVRIVER 323 Victivallis vadensis ATCC BAA-548
YP_574561   263 GAERVEGTLLGNGERTGNMDIVTLAMNLYSQGIDPELDLSRPDEIIQVVQE 313 Chromohalobacter salexigens DSM 3043
ZP_02037985 279 GAERIEATLFGNGERTGNVDMVTLAMNMYTQGVDPELDFSDINKIKAMYER 329 Bacteroides capillosus ATCC 29799
YP_392142   260 GADRVEGTLLGNGERTGNMDIVTLAMNLYSEGIDPELNLSDPDSWVPVIEE 310 Thiomicrospira crunogena XCL-2
Q8UD63      261 GADRVEGTLFGNGERTGNVDVVTLALNMYTQGVDPELDCRDIERIKAVYEY 311 Agrobacterium tumefaciens str. C58
ZP_03727786 270 GAQRVEGTLFGNGERTGNLDIVTVALNLYTQGVHPNLDFSNINAIREVYER 320 Opitutaceae bacterium TAV2
ZP_02927930 263 GADRVEGTLFGNGERTGNLDIVQVAMNLYMHGIDPGLDFSNLNALREVYER 313 Verrucomicrobium spinosum DSM 4136

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