PDBsum entry 6cs2

Viral protein/hydrolase

PDB id: 6cs2

Contents

Protein chains

891 a.a.

1076 a.a.

544 a.a.

Ligands

NAG-NAG-BMA ×9

NAG-NAG ×7

NAG-NAG-BMA-MAN ×11

NAG ×6

PDB id:

6cs2

Name:

Viral protein/hydrolase

Title:

Sars spike glycoprotein - human ace2 complex, stabilized variant, all ace2-bound particles

Structure:

Spike glycoprotein,fibritin. Chain: a, b, c. Synonym: s glycoprotein,e2,peplomer protein. Engineered: yes. Mutation: yes. Angiotensin-converting enzyme 2. Chain: d. Synonym: ace-related carboxypeptidase,angiotensin-converting enzyme homolog,aceh,metalloprotease mprot15.

Source:

Human sars coronavirus, enterobacteria phage t4. Sars-cov, bacteriophage t4. Organism_taxid: 227859, 10665. Gene: s, 2, wac, t4tp161. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293f. Homo sapiens.

Authors:

R.N.Kirchdoerfer,N.Wang,J.Pallesen,H.L.Turner,C.A.Cottrell, J.S.Mclellan,A.B.Ward

Key ref:

R.N.Kirchdoerfer et al. (2018). Stabilized coronavirus spikes are resistant to conformational changes induced by receptor recognition or proteolysis. Sci Rep, 8, 15701. PubMed id: 30356097

Date:

19-Mar-18 Release date: 11-Apr-18

Protein chains

P10104  (WAC_BPT4) -  Fibritin from Enterobacteria phage T4

Seq: 487 a.a.

Struc: 891 a.a.*

Protein chains

P59594  (SPIKE_CVHSA) -  Spike glycoprotein from Severe acute respiratory syndrome coronavirus

Seq: 1255 a.a.

Struc: 891 a.a.*

Protein chain

P10104  (WAC_BPT4) -  Fibritin from Enterobacteria phage T4

Seq: 487 a.a.

Struc: 1076 a.a.*

Protein chain

P59594  (SPIKE_CVHSA) -  Spike glycoprotein from Severe acute respiratory syndrome coronavirus

Seq: 1255 a.a.

Struc: 1076 a.a.*

Protein chain

Q9BYF1  (ACE2_HUMAN) -  Angiotensin-converting enzyme 2 from Homo sapiens

Seq: 805 a.a.

Struc: 544 a.a.

* PDB and UniProt seqs differ at 868 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: Chain D: E.C.3.4.17.- - ?????
• Enzyme class 2: Chain D: E.C.3.4.17.23 - angiotensin-converting enzyme 2.
• Reaction: angiotensin II + H2O = angiotensin-^1-7 + L-phenylalanine

angiotensin II + H2O = angiotensin-(1-7) + L-phenylalanine (Bound ligand (Het Group name = NAG) matches with 44.44% similarity)

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

Sci Rep 8:15701 (2018)

PubMed id: 30356097

Stabilized coronavirus spikes are resistant to conformational changes induced by receptor recognition or proteolysis.

R.N.Kirchdoerfer, N.Wang, J.Pallesen, D.Wrapp, H.L.Turner, C.A.Cottrell, K.S.Corbett, B.S.Graham, J.S.McLellan, A.B.Ward.

ABSTRACT

Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 as a highly transmissible pathogenic human betacoronavirus. The viral spike glycoprotein (S) utilizes angiotensin-converting enzyme 2 (ACE2) as a host protein receptor and mediates fusion of the viral and host membranes, making S essential to viral entry into host cells and host species tropism. As SARS-CoV enters host cells, the viral S is believed to undergo a number of conformational transitions as it is cleaved by host proteases and binds to host receptors. We recently developed stabilizing mutations for coronavirus spikes that prevent the transition from the pre-fusion to post-fusion states. Here, we present cryo-EM analyses of a stabilized trimeric SARS-CoV S, as well as the trypsin-cleaved, stabilized S, and its interactions with ACE2. Neither binding to ACE2 nor cleavage by trypsin at the S1/S2 cleavage site impart large conformational changes within stabilized SARS-CoV S or expose the secondary cleavage site, S2'.