2CD2,1AI9,1HFR,1CZ3,8DFR,1J3I,1QZF,1AO8,1DF7,1DHI,1VDR


Conserved Protein Domain Family
DHFR

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cd00209: DHFR 
Click on image for an interactive view with Cn3D
Dihydrofolate reductase (DHFR). Reduces 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate with NADPH as a cofactor. This is an essential step in the biosynthesis of deoxythymidine phosphate since 5,6,7,8-tetrahydrofolate is required to regenerate 5,10-methylenetetrahydrofolate which is then utilized by thymidylate synthase. Inhibition of DHFR interrupts thymidilate synthesis and DNA replication, inhibitors of DHFR (such as Methotrexate) are used in cancer chemotherapy. 5,6,7,8-tetrahydrofolate also is involved in glycine, serine, and threonine metabolism and aminoacyl-tRNA biosynthesis.
Statistics
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PSSM-Id: 238127
Aligned: 127 rows
Threshold Bit Score: 79.8744
Created: 1-Nov-2000
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
folate bindingNADP+ binding
Conserved site includes 7 residues -Click on image for an interactive view with Cn3D
Feature 1:folate binding site [chemical binding site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1        #                 #            #                                           # 
2CD2_A      7 LTLIVALTTsYGIGRSns-lpW--------KLKKEISYFKRVTsfvptfdsfesmnVVLMGRKTWESIplq-frpLKGRI 76  Pneumocystis carinii
1CZ3_B      3 VIFVLAMDVsGKIASSve--sW--------SSFEDRKNFRKITte---------igNVVMGRITFEEIgr----pLPERL 59  Thermotoga maritima
AAN46185   20 LILFIATSLdGYIARRnegidWlf-----dDADYGYSEFYSQId------------TVLMGRKTYELSmslsddpYPGCQ 82  Synechococcus elon...
NP_619399   8 IKLYIACSLdGFIARKggsvdWlteyenssETDYGYSEFYASIg------------TVLIGRKTYEQVldfgvwpYGEKK 75  Methanosarcina ace...
P78028      2 VKAIWAMDQnGLIGNGns-lpW--------RIKAELQHFRQTTlh----------qDVLMGSATYLSLpp----vFSERN 58  Mycoplasma pneumoniae
P47470      2 LIAIWAMTQeGLIGNNnt-lpW--------MIKQELAHFKKTTlf----------qALLMGRKTYESLpk----vFEKRT 58  Mycoplasma genitalium
Q9PR30      2 LKLIWCQTLnGGISKNnk-lpW--------YIKEELDHFYKTTkn----------hKIIMGKNTFDSLdq---kpLNNRT 59  Ureaplasma parvum
Q7NB76      9 IKLIWCEDLnHGIAKNnq-ipW--------KIDEELNHFHQTTtn----------hPIIMGYNTYLAMnk----iLANQA 65  Mycoplasma gallise...
NP_758074   2 FISIWCEDKnRGIGKNnk-lpW--------NIKEDLNLFKKHTln----------nTIVMGKNTFLSIgk----aLPNRK 58  Mycoplasma penetrans
P75478      2 ITLIWCQDKhFGIGRDnt-ipW--------KLTEANQHFYNTTkn----------qTVVMGYNTFQELgd----kLTDHN 58  Mycoplasma pneumoniae
Feature 1                                                       #     #              #        
2CD2_A     77 NVVITRNesldl---gngiHSAKS-LDHALellyrtygsessvqinRIFVIGGAQLYKAAMDhpklDRIMATIIYkdi-h 151 Pneumocystis carinii
1CZ3_B     60 NVVLTRRpktsn---npslVFFNGsPADVVkfleg-------kgyeRVAVIGGKTVFTEFLReklvDELFVTVEPyvf-g 128 Thermotoga maritima
AAN46185   83 IYVFSRSlteta---dpaiTVVQG-NPALWvsqlk------qqpgrNFWLVGGGQLVQQCLAadclDELILSIHPillgn 152 Synechococcus elon...
NP_619399  76 TYVFTRQkeplr--reknvEFVSGnVGEFVrrlke-------ntdeNIWLVGGSQLIRVFLEedlvQDMIVFVVPvilgs 146 Methanosarcina ace...
P78028     59 VYILTRNlnfnppdkgcltKVIHE-YENFIqpylh-------hpdkHLYICGGAQVYEQLIPr--cDALIVSTIFgky-t 127 Mycoplasma pneumoniae
P47470     59 IFLLSKDqnyrfeekgsevKVIND-FWPLIksyqa-------nkekDLFICGGKSVYEQTINe--cDQLIVSIIKkky-k 127 Mycoplasma genitalium
Q9PR30     60 NIIFSSImqtpe---desyFVTND-FQQVLnda----------kkeDIFIIGGKELFDIFLAy--aDVLIVSVLKdyy-d 122 Ureaplasma parvum
Q7NB76     66 NIVISKKhqrelk-nknelFLYSD-LKKALidf----------sivDLFIIGGKKTIEQAIKy--aDQLVISKLNady-g 130 Mycoplasma gallise...
NP_758074  59 NIVISKTldasl---ykdiEVYDD-IEQFYneyk--------nrdeSIFIIGGKSIYDYFINk--cSILYVSKLNsay-e 123 Mycoplasma penetrans
P75478     59 VVVLSKKhfeelq-nntniKVFNS-IEKLLqhh----------fnrDLYVIGGKQIFHHFIEl--aDRLIISVLPvdf-k 123 Mycoplasma pneumoniae
Feature 1                                                               
2CD2_A    152 cDVFFPlkfrdkewssVWKKekhsdleswvgtkvphGKINedg------fdYEFEMWT 203 Pneumocystis carinii
1CZ3_B    129 kGIPFFdefe---gyfPLKLle-------------mRRLNer--------gTLFLKYS 162 Thermotoga maritima
AAN46185  153 gIPLFPspf----peqRWQLvk-------------tQSYPtg--------lLQCTYHR 185 Synechococcus elongatus PCC 7942
NP_619399 147 gIPLFDrig----kevRLRMid-------------tERYEsg--------lVKLEYEI 179 Methanosarcina acetivorans C2A
P78028    128 gDKYLKvd------fsPFELtk------------eiSFAEf---------kVAYYHKI 158 Mycoplasma pneumoniae
P47470    128 gDQFLKvd------lsKFVLne-------------vVEFEe----------FNVNYYR 156 Mycoplasma genitalium
Q9PR30    123 cDLYMKvd------ynNFNLdk-------------qDVYDn----------FIVNYYS 151 Ureaplasma parvum
Q7NB76    131 cDLFVNln------ydDFSLvq-------------tKEYDq----------FVVEYWE 159 Mycoplasma gallisepticum
NP_758074 124 cDLFMDns------fdGFEIvn-------------qKEYEq---------fTFFEYRK 153 Mycoplasma penetrans
P75478    124 cNLRLKlg------ldSFELmqe----------qqhSQFKvqywhkkhperLSFNVFL 165 Mycoplasma pneumoniae

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