Structure of PDB 5x1w Chain A Binding Site BS01

Receptor Information

>5x1w Chain A (length=518) Species: 9606 (Homo sapiens)

QTQQLHAAMADTFLEHMCRLDIDSPPITARNTGIICTIGPASRSVETLKE
MIKSGMNVARLNFSHGTHEYHAETIKNVRTATESFASDPILYRPVAVALD
TKGPEIRTGLIKGSGTAEVELKKGATLKITLDNAYMEKCDENILWLDYKN
ICKVVEVGSKIYVDDGLISLQVKQKGADFLVTEVENGGSLGSKKGVNLPG
AAVDLPAVSEKDIQDLKFGVEQDVDMVFASFIRKASDVHEVRKVLGEKGK
NIKIISKIENHEGVRRFDEILEASDGIMVARGDLGIEIPAEKVFLAQKMM
IGRCNRAGKPVICATQMLESMIKKPRPTRAEGSDVANAVLDGADCIMLSG
ETAKGDYPLEAVRMQHLIAREAEAAIYHLQLFEELRRLAPITSDPTEATA
VGAVEASFKCCSGAIIVLTKSGRSAHQVARYRPRAPIIAVTRNPQTARQA
HLYRGIFPVLCKDPVQEAWAEDVDLRVNFAMNVGKARGFFKKGDVVIVLT
GWRPGSGFTNTMRVVPVP

Ligand information

• Ligand ID: FBP
• InChI: InChI=1S/C6H14O12P2/c7-4-3(1-16-19(10,11)12)18-6(9,5(4)8)2-17-20(13,14)15/h3-5,7-9H,1-2H2,(H2,10,11,12)(H2,13,14,15)/t3-,4-,5+,6-/m1/s1
• InChIKey: RNBGYGVWRKECFJ-ARQDHWQXSA-N
• SMILES:
  CACTVS 3.341: O[C@H]1[C@H](O)[C@@](O)(CO[P](O)(O)=O)O[C@@H]1CO[P](O)(O)=O
  CACTVS 3.341: O[CH]1[CH](O)[C](O)(CO[P](O)(O)=O)O[CH]1CO[P](O)(O)=O
  ACDLabs 10.04: O=P(O)(O)OCC1OC(O)(COP(=O)(O)O)C(O)C1O
  OpenEye OEToolkits 1.5.0: C(C1C(C(C(O1)(COP(=O)(O)O)O)O)O)OP(=O)(O)O
  OpenEye OEToolkits 1.5.0: C([C@@H]1[C@H]([C@@H]([C@](O1)(COP(=O)(O)O)O)O)O)OP(=O)(O)O
• Formula: C6 H14 O12 P2
• Name: 1,6-di-O-phosphono-beta-D-fructofuranose;
  BETA-FRUCTOSE-1,6-DIPHOSPHATE;
  FRUCTOSE-1,6-BISPHOSPHATE;
  1,6-di-O-phosphono-beta-D-fructose;
  1,6-di-O-phosphono-D-fructose;
  1,6-di-O-phosphono-fructose
• ChEMBL: CHEMBL97893
• DrugBank: DB04551
• ZINC: ZINC000004096694
• PDB chain: 5x1w Chain A Residue 601

Receptor-Ligand Complex Structure

Structure summary

• PDB: 5x1w Discovery and structure-guided fragment-linking of 4-(2,3-dichlorobenzoyl)-1-methyl-pyrrole-2-carboxamide as a pyruvate kinase M2 activator
• Resolution: 3.0 Å
• Binding residue (original residue number in PDB): T432 K433 S434 S437 W482 R489 G514 R516 P517 G518 S519 F521 T522
• Binding residue (residue number reindexed from 1): T419 K420 S421 S424 W469 R476 G501 R503 P504 G505 S506 F508 T509
• Annotation score: 1

Enzymatic activity

• Catalytic site (original residue number in PDB): R73 R120 K270 T328
• Catalytic site (residue number reindexed from 1): R60 R107 K257 T315
• Enzyme Commision number: 2.7.10.2: non-specific protein-tyrosine kinase.
  2.7.11.1: non-specific serine/threonine protein kinase.
  2.7.1.40: pyruvate kinase.

Gene Ontology

Molecular Function

• GO:0000287 magnesium ion binding
• GO:0003723 RNA binding
• GO:0003729 mRNA binding
• GO:0003824 catalytic activity
• GO:0004713 protein tyrosine kinase activity
• GO:0004743 pyruvate kinase activity
• GO:0005515 protein binding
• GO:0005524 ATP binding
• GO:0016301 kinase activity
• GO:0023026 MHC class II protein complex binding
• GO:0030955 potassium ion binding
• GO:0045296 cadherin binding
• GO:0046872 metal ion binding

Biological Process

• GO:0006096 glycolytic process
• GO:0006417 regulation of translation
• GO:0012501 programmed cell death
• GO:0016310 phosphorylation
• GO:0032869 cellular response to insulin stimulus
• GO:0061621 canonical glycolysis
• GO:1903672 positive regulation of sprouting angiogenesis
• GO:2000767 positive regulation of cytoplasmic translation

Cellular Component

• GO:0005576 extracellular region
• GO:0005634 nucleus
• GO:0005737 cytoplasm
• GO:0005739 mitochondrion
• GO:0005791 rough endoplasmic reticulum
• GO:0005829 cytosol
• GO:0005929 cilium
• GO:0031982 vesicle
• GO:0034774 secretory granule lumen
• GO:0062023 collagen-containing extracellular matrix
• GO:0070062 extracellular exosome
• GO:1903561 extracellular vesicle
• GO:1904813 ficolin-1-rich granule lumen

External links

• PDB: RCSB:5x1w, PDBe:5x1w, PDBj:5x1w
• PDBsum: 5x1w
• PubMed: 28511909
• UniProt: P14618|KPYM_HUMAN Pyruvate kinase PKM (Gene Name=PKM)