Structure of PDB 5v7i Chain B Binding Site BS02

Receptor Information

>5v7i Chain B (length=462) Species: 9606 (Homo sapiens)

WTGQESLSDSDPEMWELLQREKDRQCRGLELIASENFCSRAALEALGSCL
NNKYSEGYPGKRYYGGAEVVDEIELLCQRRALEAFDLDPAQWGVNVQPYS
GSPANLAVYTALLQPHDRIMGLDLPDGGHLTHGYMSDVKRISATSIFFES
MPYKLNPKTGLIDYNQLALTARLFRPRLIIAGTSAYARLIDYARMREVCD
EVKAHLLADMAHISGLVAAKVIPSPFKHADIVTTTTHKTLRGARSGLIFY
RKGVKAVDPKTGREIPYTFEDRINFAVFPSLQGGPHNHAIAAVAVALKQA
CTPMFREYSLQVLKNARAMADALLERGYSLVSGGTDNHLVLVDLRPKGLD
GARAERVLELVSITANKNTCPGDRSAITPGGLRLGAPALTSRQFREDDFR
RVVDFIDEGVNIGLEVKSKTAKLQDFKSFLLKDSETSQRLANLRQRVEQF
ARAFPMPGFDEH

Ligand information

• Ligand ID: 8Z1
• InChI: InChI=1S/C22H24F3N5O/c1-12(2)21(17(11-26)19(27)31-20-18(21)13(3)28-29-20)14-8-15(22(23,24)25)10-16(9-14)30-6-4-5-7-30/h8-10,12H,4-7,27H2,1-3H3,(H,28,29)/t21-/m0/s1
• InChIKey: NOKJZHRLDAOFCV-NRFANRHFSA-N
• SMILES:
  OpenEye OEToolkits 2.0.6: Cc1c2c([nH]n1)OC(=C(C2(c3cc(cc(c3)N4CCCC4)C(F)(F)F)C(C)C)C#N)N
  CACTVS 3.385: CC(C)[C]1(c2cc(cc(c2)C(F)(F)F)N3CCCC3)C(=C(N)Oc4[nH]nc(C)c14)C#N
  CACTVS 3.385: CC(C)[C@]1(c2cc(cc(c2)C(F)(F)F)N3CCCC3)C(=C(N)Oc4[nH]nc(C)c14)C#N
  ACDLabs 12.01: N#CC=1C(c2c(OC=1N)nnc2C)(c3cc(C(F)(F)F)cc(c3)N4CCCC4)C(C)C
  OpenEye OEToolkits 2.0.6: Cc1c2c([nH]n1)OC(=C([C@@]2(c3cc(cc(c3)N4CCCC4)C(F)(F)F)C(C)C)C#N)N
• Formula: C22 H24 F3 N5 O
• Name: (4R)-6-amino-3-methyl-4-(propan-2-yl)-4-[3-(pyrrolidin-1-yl)-5-(trifluoromethyl)phenyl]-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile
• PDB chain: 5v7i Chain B Residue 601

Receptor-Ligand Complex Structure

Structure summary

• PDB: 5v7i Human SHMT inhibitors reveal defective glycine import as a targetable metabolic vulnerability of diffuse large B-cell lymphoma.
• Resolution: 2.47 Å
• Binding residue (original residue number in PDB): L166 G170 H171 S226 K409
• Binding residue (residue number reindexed from 1): L124 G128 H129 S184 K367
• Annotation score: 1
• Binding affinity: PDBbind-CN: -logKd/Ki=7.18,IC50=66nM
  BindingDB: IC50=13.0nM

Enzymatic activity

• Catalytic site (original residue number in PDB): Y96 E98 D251 T277 K280 R286
• Catalytic site (residue number reindexed from 1): Y54 E56 D209 T235 K238 R244
• Enzyme Commision number: 2.1.2.1: glycine hydroxymethyltransferase.

Gene Ontology

Molecular Function

• GO:0003682 chromatin binding
• GO:0004372 glycine hydroxymethyltransferase activity
• GO:0005515 protein binding
• GO:0008732 L-allo-threonine aldolase activity
• GO:0016597 amino acid binding
• GO:0016740 transferase activity
• GO:0030170 pyridoxal phosphate binding
• GO:0042802 identical protein binding

Biological Process

• GO:0002082 regulation of oxidative phosphorylation
• GO:0006544 glycine metabolic process
• GO:0006545 glycine biosynthetic process
• GO:0006563 L-serine metabolic process
• GO:0006564 L-serine biosynthetic process
• GO:0006730 one-carbon metabolic process
• GO:0008284 positive regulation of cell population proliferation
• GO:0019264 glycine biosynthetic process from serine
• GO:0034340 response to type I interferon
• GO:0035999 tetrahydrofolate interconversion
• GO:0046653 tetrahydrofolate metabolic process
• GO:0051262 protein tetramerization
• GO:0051289 protein homotetramerization
• GO:0070129 regulation of mitochondrial translation
• GO:0070536 protein K63-linked deubiquitination
• GO:1903715 regulation of aerobic respiration

Cellular Component

• GO:0005634 nucleus
• GO:0005737 cytoplasm
• GO:0005739 mitochondrion
• GO:0005743 mitochondrial inner membrane
• GO:0005759 mitochondrial matrix
• GO:0015630 microtubule cytoskeleton
• GO:0042645 mitochondrial nucleoid
• GO:0070062 extracellular exosome
• GO:0070552 BRISC complex

External links

• PDB: RCSB:5v7i, PDBe:5v7i, PDBj:5v7i
• PDBsum: 5v7i
• PubMed: 29073064
• UniProt: P34897|GLYM_HUMAN Serine hydroxymethyltransferase, mitochondrial (Gene Name=SHMT2)