Structure of PDB 6dug Chain A Binding Site BS01

Receptor Information

>6dug Chain A (length=556) Species: 11678 (Human immunodeficiency virus type 1 BH10)

MVPISPIETVPVKLKPGMDGPKVKQWPLTEEKIKALVEICTEMEKEGKIS
KIGPENPYNTPVFAIKKKDSTKWRKLVDFRELNKRTQDFWEVQLGIPHPA
GLPKKKSVTVLDVGDAYFSVPLDEDFRKYTAFTIPSINNETPGIRYQYNV
LPQGWKGSPAIFQSSMTKILEPFAAQNPDIVIYQYMDDLYVGSDLEIGQH
RTKIEELRQHLLRWGLTTPDKKHQKEPPFLWMGYELHPDKWTVQPIVLPE
KDSWTVNDIQKLVGKLNWASQIYPGIKVRQLSKLLRGTKALTEVIPLTEE
AELELAENREILKEPVHGVYYDPSKDLIAEIQKQGQGQWTYQIYQEPFKN
LKTGKYARMRGAHTNDVKQLTEAVQKITTESIVIWGKTPKFKLPIQKETW
ETWWTEYWQATWIPEWEFVNTPPLVKLWYQLEKEPIVGAETFYVDGAANR
ETKLGKAGYVTNKGRQKVVPLTNTTNQKTELQAIYLALQDSGLEVNIVTD
SQYALGIIQAQPDKSESELVNQIIEQLIKKEKVYLAWVPAHKGIGGNEQV
DKLVSA

Ligand information

• Ligand ID: K5C
• InChI: InChI=1S/C29H30N6O3S2/c1-19-16-22(4-3-12-30)17-20(2)26(19)38-28-27-25(11-15-39-27)33-29(34-28)32-23-9-13-35(14-10-23)18-21-5-7-24(8-6-21)40(31,36)37/h3-8,11,15-17,23H,9-10,13-14,18H2,1-2H3,(H2,31,36,37)(H,32,33,34)/b4-3+
• InChIKey: GVCHBMCBPBRORW-ONEGZZNKSA-N
• SMILES:
  OpenEye OEToolkits 2.0.6: Cc1cc(cc(c1Oc2c3c(ccs3)nc(n2)NC4CCN(CC4)Cc5ccc(cc5)S(=O)(=O)N)C)C=CC#N
  OpenEye OEToolkits 2.0.6: Cc1cc(cc(c1Oc2c3c(ccs3)nc(n2)NC4CCN(CC4)Cc5ccc(cc5)S(=O)(=O)N)C)/C=C/C#N
  CACTVS 3.385: Cc1cc(C=CC#N)cc(C)c1Oc2nc(NC3CCN(CC3)Cc4ccc(cc4)[S](N)(=O)=O)nc5ccsc25
  CACTVS 3.385: Cc1cc(\C=C\C#N)cc(C)c1Oc2nc(NC3CCN(CC3)Cc4ccc(cc4)[S](N)(=O)=O)nc5ccsc25
  ACDLabs 12.01: Cc1cc(\C=C\C#N)cc(C)c1Oc3c2c(ccs2)nc(n3)NC5CCN(Cc4ccc(cc4)S(N)(=O)=O)CC5
• Formula: C29 H30 N6 O3 S2
• Name: 4-({4-[(4-{4-[(E)-2-cyanoethenyl]-2,6-dimethylphenoxy}thieno[3,2-d]pyrimidin-2-yl)amino]piperidin-1-yl}methyl)benzene-1-sulfonamide
• ChEMBL: CHEMBL4094163
• PDB chain: 6dug Chain A Residue 601

Receptor-Ligand Complex Structure

Structure summary

• PDB: 6dug Structural basis for potent and broad inhibition of HIV-1 RT by thiophene[3,2-d]pyrimidine non-nucleoside inhibitors.
• Resolution: 2.225 Å
• Binding residue (original residue number in PDB): L100 P101 K103 K104 S105 V179 Y181 Y188 F227 W229 P236 Y318
• Binding residue (residue number reindexed from 1): L102 P103 K105 K106 S107 V181 Y183 Y190 F229 W231 P238 Y320
• Annotation score: 1
• Binding affinity: MOAD: ic50=5.4nM
  PDBbind-CN: -logKd/Ki=8.27,IC50=5.4nM

Enzymatic activity

• Enzyme Commision number: 2.7.7.-
  2.7.7.49: RNA-directed DNA polymerase.
  2.7.7.7: DNA-directed DNA polymerase.
  3.1.-.-
  3.1.13.2: exoribonuclease H.
  3.1.26.13: retroviral ribonuclease H.
  3.4.23.16: HIV-1 retropepsin.

Gene Ontology

Molecular Function

• GO:0003676 nucleic acid binding
• GO:0003964 RNA-directed DNA polymerase activity
• GO:0004523 RNA-DNA hybrid ribonuclease activity

Biological Process

• GO:0006278 RNA-templated DNA biosynthetic process

External links

• PDB: RCSB:6dug, PDBe:6dug, PDBj:6dug
• PDBsum: 6dug
• PubMed: 30044217
• UniProt: P03366|POL_HV1B1 Gag-Pol polyprotein (Gene Name=gag-pol)