PDBsum entry 3d23

Hydrolase/hydrolase inhibitor

PDB id: 3d23

Contents

Protein chains

301 a.a. *

Ligands

02J-ALA-VAL-LEU-PJE-010 ×4

Waters ×208

* Residue conservation analysis

PDB id:

3d23

Name:

Hydrolase/hydrolase inhibitor

Title:

Main protease of hcov-hku1

Structure:

3c-like proteinase. Chain: b, a, c, d. Engineered: yes. N-[(5-methylisoxazol-3-yl)carbonyl]alanyl-l-valyl-n~1~- ((1r,2z)-4-(benzyloxy)-4-oxo-1-{[(3r)-2-oxopyrrolidin-3- yl]methyl}but-2-enyl)-l-leucinamide. Chain: h, f, e, g. Engineered: yes

Source:

Human coronavirus. Hcov-hku1. Organism_taxid: 443239. Strain: hku1. Gene: rep. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Synthetic construct.

Resolution:

2.50Å R-factor: 0.232 R-free: 0.285

Authors:

Q.Zhao,C.Chen,S.Li,Y.Zou

Key ref:

Q.Zhao et al. (2008). Structure of the main protease from a global infectious human coronavirus, HCoV-HKU1. J Virol, 82, 8647-8655. PubMed id: 18562531

Date:

07-May-08 Release date: 16-Sep-08

Protein chains

P0C6U3  (R1A_CVHN1) -  Replicase polyprotein 1a from Human coronavirus HKU1 (isolate N1)

Seq: 4471 a.a.

Struc: 301 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class 1: E.C.2.7.7.50 - mRNA guanylyltransferase.
• Reaction: a 5'-end diphospho-ribonucleoside in mRNA + GTP + H⁺ = a 5'-end (5'-triphosphoguanosine)-ribonucleoside in mRNA + diphosphate
• Enzyme class 2: E.C.3.4.19.12 - ubiquitinyl hydrolase 1.
• Reaction: Thiol-dependent hydrolysis of ester, thiolester, 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).
• Enzyme class 3: E.C.3.4.22.- - ?????
• Enzyme class 4: E.C.3.4.22.69 - Sars coronavirus main proteinase.

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

J Virol 82:8647-8655 (2008)

PubMed id: 18562531

Structure of the main protease from a global infectious human coronavirus, HCoV-HKU1.

Q.Zhao, S.Li, F.Xue, Y.Zou, C.Chen, M.Bartlam, Z.Rao.

ABSTRACT

The newly emergent human coronavirus HKU1 (HCoV-HKU1) was first identified in Hong Kong in 2005. Infection by HCoV-HKU1 occurs worldwide and causes syndromes such as the common cold, bronchitis, and pneumonia. The CoV main protease (M(pro)), which is a key enzyme in viral replication via the proteolytic processing of the replicase polyproteins, has been recognized as an attractive target for rational drug design. In this study, we report the structure of HCoV-HKU1 M(pro) in complex with a Michael acceptor, inhibitor N3. The structure of HCoV-HKU1 provides a high-quality model for group 2A CoVs, which are distinct from group 2B CoVs such as severe acute respiratory syndrome CoV. The structure, together with activity assays, supports the relative conservation at the P1 position that was discovered by sequencing the HCoV-HKU1 genome. Combined with structural data from other CoV M(pro)s, the HCoV-HKU1 M(pro) structure reported here provides insights into both substrate preference and the design of antivirals targeting CoVs.