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(-) Description

Title :  HUMAN PFKFB3 IN COMPLEX WITH A PYRROLOPYRIMIDONE COMPOUND
 
Authors :  S. A. Stgallay, N. Bennett, S. Critchlow, G. Davies, J. E. Debreczeni, N G. Holdgate, N. P. Jones, L. Leach, S. Maman, S. Mcloughlin, M. Preston L. Rigoreau, A. Thomas, G. Walker, J. Walsch, R. A. Ward, E. Wheatley, J
Date :  29 Oct 14  (Deposition) - 20 Jan 16  (Release) - 20 Jan 16  (Revision)
Method :  X-RAY DIFFRACTION
Resolution :  3.00
Chains :  Asym. Unit :  A
Biol. Unit 1:  A  (2x)
Keywords :  Transferase, Sugar Kinase, Warburg Effect, Oncology (Keyword Search: [Gene Ontology, PubMed, Web (Google))
 
Reference :  S. A. Stgallay, N. Bennett, S. Critchlow, G. Davies, J. E. Debreczeni, N. Evans, G. Holdgate, N. P. Jones, L. Leach, S. Maman, S. Mcloughlin, M. Preston, L. Rigoreau, A. Thomas, G. Walker, J. Walsch, R. A. Ward, E. Wheatley, J. Winter
Identifying A Novel Series Of Pfkfb3 Inhibitors As A Metabolic Approach To Treating Cancer From Hts, Biophysical And Biochemical Methods
To Be Published
PubMed: search

(-) Compounds

Molecule 1 - 6-PHOSPHOFRUCTO-2-KINASE/FRUCTOSE-2,6-BISPHOSPHATASE 3
    ChainsA
    EC Number2.7.1.105, 3.1.3.46
    EngineeredYES
    Expression SystemESCHERICHIA COLI
    Expression System StrainBL21
    Expression System Taxid511693
    Organism CommonHUMAN
    Organism ScientificHOMO SAPIENS
    Organism Taxid9606
    Synonym6PF-2-K/FRU-2,6-P2ASE 3,PFKFBPASE 3 PFKFB3,6PF-2-K/FRU-2,6-P2ASE BRAIN/PLACENTA-TYPE ISOZYME, RENAL CARCINOMA ANTIGEN NY-REN-56,IPFK-2,6-PHOSPHOFRUCTO-2-KINASE, FRUCTOSE-2,6-BISPHOSPHATASE

 Structural Features

(-) Chains, Units

  1
Asymmetric Unit A
Biological Unit 1 (2x)A

Summary Information (see also Sequences/Alignments below)

(-) Ligands, Modified Residues, Ions  (4, 4)

Asymmetric Unit (4, 4)
No.NameCountTypeFull Name
1BKI1Ligand/Ion5-(4-BROMOPHENYL)-7-PHENYL-3,7-DIHYDRO-4H-PYRROLO[2,3-D]PYRIMIDIN-4-ONE
2F6P1Ligand/IonFRUCTOSE-6-PHOSPHATE
3PHS1Ligand/IonPHOSPHONIC ACID
4PO41Ligand/IonPHOSPHATE ION
Biological Unit 1 (4, 8)
No.NameCountTypeFull Name
1BKI2Ligand/Ion5-(4-BROMOPHENYL)-7-PHENYL-3,7-DIHYDRO-4H-PYRROLO[2,3-D]PYRIMIDIN-4-ONE
2F6P2Ligand/IonFRUCTOSE-6-PHOSPHATE
3PHS2Ligand/IonPHOSPHONIC ACID
4PO42Ligand/IonPHOSPHATE ION

(-) Sites  (4, 4)

Asymmetric Unit (4, 4)
No.NameEvidenceResiduesDescription
1AC1SOFTWAREPRO A:43 , ALA A:44 , ARG A:45 , GLY A:46 , LYS A:47 , THR A:48 , ASN A:163 , LYS A:168 , HOH A:2009BINDING SITE FOR RESIDUE PO4 A1446
2AC2SOFTWAREARG A:252 , HIS A:253 , ASN A:259 , GLU A:322 , HIS A:387 , GLN A:388 , F6P A:1448BINDING SITE FOR RESIDUE PHS A1447
3AC3SOFTWAREILE A:264 , GLY A:265 , GLU A:322 , TYR A:333 , ARG A:347 , LYS A:351 , TYR A:362 , GLN A:388 , ARG A:392 , THR A:440 , PHS A:1447BINDING SITE FOR RESIDUE F6P A1448
4AC4SOFTWAREALA A:44 , ARG A:45 , GLY A:46 , TYR A:49 , ILE A:50 , SER A:152 , VAL A:159 , ASN A:163 , GLU A:166 , VAL A:214 , VAL A:217 , LEU A:238 , VAL A:243BINDING SITE FOR RESIDUE BKI A1449

(-) SS Bonds  (0, 0)

(no "SS Bond" information available for 4D4J)

(-) Cis Peptide Bonds  (1, 1)

Asymmetric Unit
No.Residues
1Gly A:27 -Pro A:28

 Sequence-Structure Mapping

(-) SAPs(SNPs)/Variants  (0, 0)

(no "SAP(SNP)/Variant" information available for 4D4J)

(-) PROSITE Motifs  (0, 0)

(no "PROSITE Motif" information available for 4D4J)

(-) Exons   (0, 0)

(no "Exon" information available for 4D4J)

(-) Sequences/Alignments

Asymmetric Unit
   Reformat: Number of residues per line =  ('0' or empty: single-line sequence representation)
  Number of residues per labelling interval =   
  UniProt sequence: complete  aligned part    
   Show mapping: SCOP domains CATH domains Pfam domains Secondary structure (by author)
SAPs(SNPs) PROSITE motifs Exons
(details for a mapped element are shown in a popup box when the mouse pointer rests over it)
Chain A from PDB  Type:PROTEIN  Length:442
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
               SCOP domains ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- SCOP domains
               CATH domains ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- CATH domains
               Pfam domains ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Pfam domains
         Sec.struct. author ...eee......eee................eeeeee.....hhhhhhhhhhhhhhhh...eeeeehhhhhhhhh....hhhhhh..hhhhhhhhhhhhhhhhhhhhhhhhhh...eeeee....hhhhhhhhhhhhhhh..eeeeeeee..hhhhhhhhhhhhh..hhhhh..hhhhhhhhhhhhhhhhhh...............eeeee....eeeee...hhhhhhhhhhhhhh......eeeee...hhhhhhh........hhhhhhhhhhhhhhhhhh.....eeee..hhhhhhhhhh.....ee.hhhh...hhhhh..hhhhhhhhhhhhhhhhhhh..........hhhhhhhhhhhhhhhhhhh..eeeeehhhhhhhhhhhhh.....hhhhh.....eeeeeeee..eeeeeeee............. Sec.struct. author
                 SAPs(SNPs) ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- SAPs(SNPs)
                    PROSITE ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- PROSITE
                 Transcript ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Transcript
                 4d4j A   1 PLELTQSRVQKIWVPVDHRPSLPRSCGPNSPTVIVMVGLPARGKTYISKKLTRYLNWIGVPTKVFNVGEYRREAVKQYSSYNFFRPDNEEAMKVRKQCALAALRDVKSYLAKEGGQIAVFDATNTTRERRHMILHFAKENDFKAFFIESVCDDPTVVASNIMEVKISSPDYKDCNSAEAMDDFMKRISCYEASYQPLDPDKCDRDLSLIKVIDVGRRFLVNRVQDHIQSRIVYYLMNIHVQPRTIYLCRHGENEHNLQGRIGGDSGLSSRGKKFASALSKFVEEQNLKDLRVWTSQLKSTIQTAEALRLPYEQWKALNEIDAGVCEELTYEEIRDTYPEEYALREQDKYYYRYPTGESYQDLVQRLEPVIMELERQENVLVICHQAVLRCLLAYFLDKSAEEMPYLKCPLHTVLKLTPVAYGCRVESIYLNVESVCTHRERS 445
                                    10        20       |33        43        53        63        73        83        93       103       113       123       133       143       153       163       173       183       193       203       213       223       233       243       253       263       273       283       293       303       313       323       333       343       353       363       373       383       393       403       413       423       433       443  
                                                      28|                                                                                                                                                                                                                                                                                                                                                                                                                             
                                                       32                                                                                                                                                                                                                                                                                                                                                                                                                             

   Legend:   → Mismatch (orange background)
  - → Gap (green background, '-', border residues have a numbering label)
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  x → Chemical Group (purple background, 'x', labelled with number + name, e.g. ACE or NH2)
  extra numbering lines below/above indicate numbering irregularities and modified residue names etc., number ends below/above '|'

 Classification and Annotation

(-) SCOP Domains  (0, 0)

(no "SCOP Domain" information available for 4D4J)

(-) CATH Domains  (0, 0)

(no "CATH Domain" information available for 4D4J)

(-) Pfam Domains  (0, 0)

(no "Pfam Domain" information available for 4D4J)

(-) Gene Ontology  (18, 18)

Asymmetric Unit(hide GO term definitions)

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 Related Entries

(-) Entries Sharing at Least One Protein Chain (UniProt ID)

UniProtKB/Swiss-Prot
        F263_HUMAN | Q168752axn 2dwo 2dwp 2i1v 3qpu 3qpv 3qpw 4d4k 4d4l 4d4m 4ma4 5ajv 5ajw 5ajx 5ajy 5ajz 5ak0

(-) Related Entries Specified in the PDB File

4d4k HUMAN PFKFB3 IN COMPLEX WITH A PYRROLOPYRIMIDONE COMPOUND
4d4l HUMAN PFKFB3 IN COMPLEX WITH A PYRROLOPYRIMIDONE COMPOUND
4d4m HUMAN PFKFB3 IN COMPLEX WITH A PYRROLOPYRIMIDONE COMPOUND