X-ray diffraction
1.69Å resolution

Group deposition SARS-CoV-2 main protease in complex with inhibitors from the COVID Moonshot -- Crystal Structure of SARS-CoV-2 main protease in complex with ALP-POS-ce760d3f-4 (Mpro-x12723)

Primary publication:
Open science discovery of potent noncovalent SARS-CoV-2 main protease inhibitors.
Boby ML, Fearon D, Ferla M, Filep M, Koekemoer L, Robinson MC, Chodera JD, Lee AA, London N, von Delft A, von Delft F, Achdout H, Aimon A, Alonzi DS, Arbon R, Aschenbrenner JC, Balcomb BH, Bar-David E, Barr H, Ben-Shmuel A, Bennett J, Bilenko VA, Borden B, Boulet P, Bowman GR, Brewitz L, Brun J, Bvnbs S, Calmiano M, Carbery A, Carney DW, Cattermole E, Chang E, Chernyshenko E, Clyde A, Coffland JE, Cohen G, Cole JC, Contini A, Cox L, Croll TI, Cvitkovic M, De Jonghe S, Dias A, Donckers K, Dotson DL, Douangamath A, Duberstein S, Dudgeon T, Dunnett LE, Eastman P, Erez N, Eyermann CJ, Fairhead M, Fate G, Fedorov O, Fernandes RS, Ferrins L, Foster R, Foster H, Fraisse L, Gabizon R, García-Sastre A, Gawriljuk VO, Gehrtz P, Gileadi C, Giroud C, Glass WG, Glen RC, Glinert I, Godoy AS, Gorichko M, Gorrie-Stone T, Griffen EJ, Haneef A, Hassell Hart S, Heer J, Henry M, Hill M, Horrell S, Huang QYJ, Huliak VD, Hurley MFD, Israely T, Jajack A, Jansen J, Jnoff E, Jochmans D, John T, Kaminow B, Kang L, Kantsadi AL, Kenny PW, Kiappes JL, Kinakh SO, Kovar B, Krojer T, La VNT, Laghnimi-Hahn S, Lefker BA, Levy H, Lithgo RM, Logvinenko IG, Lukacik P, Macdonald HB, MacLean EM, Makower LL, Malla TR, Marples PG, Matviiuk T, McCorkindale W, McGovern BL, Melamed S, Melnykov KP, Michurin O, Miesen P, Mikolajek H, Milne BF, Minh D, Morris A, Morris GM, Morwitzer MJ, Moustakas D, Mowbray CE, Nakamura AM, Neto JB, Neyts J, Nguyen L, Noske GD, Oleinikovas V, Oliva G, Overheul GJ, Owen CD, Pai R, Pan J, Paran N, Payne AM, Perry B, Pingle M, Pinjari J, Politi B, Powell A, Pšenák V, Pulido I, Puni R, Rangel VL, Reddi RN, Rees P, Reid SP, Reid L, Resnick E, Ripka EG, Robinson RP, Rodriguez-Guerra J, Rosales R, Rufa DA, Saar K, Saikatendu KS, Salah E, Schaller D, Scheen J, Schiffer CA, Schofield CJ, Shafeev M, Shaikh A, Shaqra AM, Shi J, Shurrush K, Singh S, Sittner A, Sjö P, Skyner R, Smalley A, Smeets B, Smilova MD, Solmesky LJ, Spencer J, Strain-Damerell C, Swamy V, Tamir H, Taylor JC, Tennant RE, Thompson W, Thompson A, Tomásio S, Tomlinson CWE, Tsurupa IS, Tumber A, Vakonakis I, van Rij RP, Vangeel L, Varghese FS, Vaschetto M, Vitner EB, Voelz V, Volkamer A, Walsh MA, Ward W, Weatherall C, Weiss S, White KM, Wild CF, Witt KD, Wittmann M, Wright N, Yahalom-Ronen Y, Yilmaz NK, Zaidmann D, Zhang I, Zidane H, Zitzmann N, Zvornicanin SN
Science 382 eabo7201 (2023)
PMID: 37943932

Function and Biology Details

Reactions catalysed:
S-adenosyl-L-methionine + a 5'-(5'-triphosphoguanosine)-[mRNA] = S-adenosyl-L-homocysteine + a 5'-(N(7)-methyl 5'-triphosphoguanosine)-[mRNA]
S-adenosyl-L-methionine + a 5'-(N(7)-methyl 5'-triphosphoguanosine)-(ribonucleotide)-[mRNA] = S-adenosyl-L-homocysteine + a 5'-(N(7)-methyl 5'-triphosphoguanosine)-(2'-O-methyl-ribonucleotide)-[mRNA]
Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1)
GTP + a 5'-diphospho-[mRNA] = diphosphate + a 5'-(5'-triphosphoguanosine)-[mRNA]
Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).
TSAVLQ-|-SGFRK-NH(2) and SGVTFQ-|-GKFKK the two peptides corresponding to the two self-cleavage sites of the SARS 3C-like proteinase are the two most reactive peptide substrates. The enzyme exhibits a strong preference for substrates containing Gln at P1 position and Leu at P2 position.
ATP + H(2)O = ADP + phosphate
Biochemical function:
Biological process:
Cellular component:
  • not assigned

Structure analysis Details

Assembly composition:
homo dimer (preferred)
PDBe Complex ID:
PDB-CPX-145080 (preferred)
Entry contents:
1 distinct polypeptide molecule
3C-like proteinase nsp5 Chain: A
Molecule details ›
Chain: A
Length: 306 amino acids
Theoretical weight: 33.83 KDa
Source organism: Severe acute respiratory syndrome coronavirus 2
Expression system: Escherichia coli
  • Canonical: P0DTD1 (Residues: 3264-3569; Coverage: 4%)
Gene names: 1a-1b, rep
Sequence domains: Coronavirus endopeptidase C30

Ligands and Environments

2 bound ligands:
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: DIAMOND BEAMLINE I04-1
Spacegroup: C2
Unit cell:
a: 112.05Å b: 52.52Å c: 44.45Å
α: 90° β: 103° γ: 90°
R R work R free
0.188 0.187 0.22
Expression system: Escherichia coli