7ekc

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Structure of SARS-CoV-2 Gamma variant spike receptor-binding domain complexed with human ACE2

Structural highlights

7ekc is a 2 chain structure with sequence from Homo sapiens and Severe acute respiratory syndrome coronavirus 2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.8Å
Ligands:NAG, ZN
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ACE2_HUMAN Carboxypeptidase which converts angiotensin I to angiotensin 1-9, a peptide of unknown function, and angiotensin II to angiotensin 1-7, a vasodilator. Also able to hydrolyze apelin-13 and dynorphin-13 with high efficiency. May be an important regulator of heart function. In case of human coronaviruses SARS and HCoV-NL63 infections, serve as functional receptor for the spike glycoprotein of both coronaviruses.[1] [2] [3]

Publication Abstract from PubMed

Multiple SARS-CoV-2 variants of concern (VOCs) have been emerging and some have been linked to an increase in case numbers globally. However, there is yet a lack of understanding of the molecular basis for the interactions between the human ACE2 (hACE2) receptor and these VOCs. Here we examined several VOCs including Alpha, Beta, and Gamma, and demonstrate that five variants receptor-binding domain (RBD) increased binding affinity for hACE2, and four variants pseudoviruses increased entry into susceptible cells. Crystal structures of hACE2-RBD complexes help identify the key residues facilitating changes in hACE2 binding affinity. Additionally, soluble hACE2 protein efficiently prevent most of the variants pseudoviruses. Our findings provide important molecular information and may help the development of novel therapeutic and prophylactic agents targeting these emerging mutants.

Molecular insights into receptor binding of recent emerging SARS-CoV-2 variants.,Han P, Su C, Zhang Y, Bai C, Zheng A, Qiao C, Wang Q, Niu S, Chen Q, Zhang Y, Li W, Liao H, Li J, Zhang Z, Cho H, Yang M, Rong X, Hu Y, Huang N, Yan J, Wang Q, Zhao X, Gao GF, Qi J Nat Commun. 2021 Oct 20;12(1):6103. doi: 10.1038/s41467-021-26401-w. PMID:34671049[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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See Also

References

  1. ↑ Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, Breitbart RE, Acton S. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res. 2000 Sep 1;87(5):E1-9. PMID:10969042
  2. ↑ Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem. 2000 Oct 27;275(43):33238-43. PMID:10924499 doi:http://dx.doi.org/10.1074/jbc.M002615200
  3. ↑ Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003 Nov 27;426(6965):450-4. PMID:14647384 doi:http://dx.doi.org/10.1038/nature02145
  4. ↑ Han P, Su C, Zhang Y, Bai C, Zheng A, Qiao C, Wang Q, Niu S, Chen Q, Zhang Y, Li W, Liao H, Li J, Zhang Z, Cho H, Yang M, Rong X, Hu Y, Huang N, Yan J, Wang Q, Zhao X, Gao GF, Qi J. Molecular insights into receptor binding of recent emerging SARS-CoV-2 variants. Nat Commun. 2021 Oct 20;12(1):6103. PMID:34671049 doi:10.1038/s41467-021-26401-w

Contents


PDB ID 7ekc

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OCA

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