Structure of PDB 5wkl Chain A Binding Site BS01

Receptor Information

>5wkl Chain A (length=303) Species: 1335626 (Middle East respiratory syndrome-related coronavirus)

HHSGLVKMSHPSGDVEACMVQVTCGSMTLNGLWLDNTVWCPRHVMCPADQ
LSDPNYDALLISMTNHSFSVQKHIANLRVVGHAMQGTLLKLTVDVANPST
PAYTFTTVKPGAAFSVLACYNGRPTGTFTVVMRPNYTIKGSFLCGSCGSV
GYTKEGSVINFCYMHQMELANGTHTGSAFDGTMYGAFMDKQVHQVQLTDK
YCSVNVVAWLYAAILNGCAWFVKPNRTSVVSFNEWALANQFTEFVGTQSV
DMLAVKTGVAIEQLLYAIQQLYTGFQGKQILGSTMLEDEFTPEDVNMQIM
GVV

Ligand information

• Ligand ID: AVY
• InChI: InChI=1S/C31H48N4O10S/c1-20(2)17-23(26(37)33-24(27(38)46(41,42)43)18-22-11-14-32-25(22)36)34-28(39)44-31(19-21-9-7-6-8-10-21)12-15-35(16-13-31)29(40)45-30(3,4)5/h6-10,20,22-24,27,38H,11-19H2,1-5H3,(H,32,36)(H,33,37)(H,34,39)(H,41,42,43)/t22-,23-,24-,27+/m0/s1
• InChIKey: PJEUBFINPIVQHS-IPVQETTRSA-N
• SMILES:
  OpenEye OEToolkits 2.0.6: CC(C)CC(C(=O)NC(CC1CCNC1=O)C(O)S(=O)(=O)O)NC(=O)OC2(CCN(CC2)C(=O)OC(C)(C)C)Cc3ccccc3
  OpenEye OEToolkits 2.0.6: CC(C)C[C@@H](C(=O)N[C@@H](C[C@@H]1CCNC1=O)[C@H](O)S(=O)(=O)O)NC(=O)OC2(CCN(CC2)C(=O)OC(C)(C)C)Cc3ccccc3
  ACDLabs 12.01: C(CC1CCNC1=O)(C(S(O)(=O)=O)O)NC(C(CC(C)C)NC(=O)OC3(Cc2ccccc2)CCN(CC3)C(=O)OC(C)(C)C)=O
  CACTVS 3.385: CC(C)C[CH](NC(=O)OC1(CCN(CC1)C(=O)OC(C)(C)C)Cc2ccccc2)C(=O)N[CH](C[CH]3CCNC3=O)[CH](O)[S](O)(=O)=O
  CACTVS 3.385: CC(C)C[C@H](NC(=O)OC1(CCN(CC1)C(=O)OC(C)(C)C)Cc2ccccc2)C(=O)N[C@@H](C[C@@H]3CCNC3=O)[C@H](O)[S](O)(=O)=O
• Formula: C31 H48 N4 O10 S
• Name: (1R,2S)-2-{[N-({[4-benzyl-1-(tert-butoxycarbonyl)piperidin-4-yl]oxy}carbonyl)-L-leucyl]amino}-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propane-1-sulfonic acid;
  bound form
• PDB chain: 5wkl Chain A Residue 401

Receptor-Ligand Complex Structure

Structure summary

• PDB: 5wkl Structure-guided design of potent and permeable inhibitors of MERS coronavirus 3CL protease that utilize a piperidine moiety as a novel design element.
• Resolution: 1.85 Å
• Binding residue (original residue number in PDB): H41 F143 C145 C148 H166 Q167 M168 E169 D190 Q192
• Binding residue (residue number reindexed from 1): H43 F142 C144 C147 H165 Q166 M167 E168 D189 Q191
• Annotation score: 1
• Binding affinity: PDBbind-CN: -logKd/Ki=6.15,IC50=0.7uM

Enzymatic activity

• Enzyme Commision number: 2.7.7.50: mRNA guanylyltransferase.
  3.4.19.12: ubiquitinyl hydrolase 1.
  3.4.22.-
  3.4.22.69: SARS coronavirus main proteinase.

Gene Ontology

Molecular Function

• GO:0008233 peptidase activity

Biological Process

• GO:0019082 viral protein processing

External links

• PDB: RCSB:5wkl, PDBe:5wkl, PDBj:5wkl
• PDBsum: 5wkl
• PubMed: 29544147
• UniProt: K9N638|R1A_MERS1 Replicase polyprotein 1a (Gene Name=1a)