The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
ACE2 X-Ray Structures Reveal a Large Hinge-bending Motion Important for Inhibitor Binding and Catalysis
Open accessAbstract
The angiotensin-converting enzyme (ACE)-related carboxypeptidase, ACE2, is a type I integral membrane protein of 805 amino acids that contains one HEXXH + E zinc-binding consensus sequence. ACE2 has been implicated in the regulation of heart function and also as a functional receptor for the coronavirus that causes the severe acute respiratory syndrome (SARS). To gain further insights into this enzyme, the first crystal structures of the native and inhibitor-bound forms of the ACE2 extracellular domains were solved to 2.2- and 3.0-A resolution, respectively. Comparison of these structures revealed a large inhibitor-dependent hinge-bending movement of one catalytic subdomain relative to the other ( approximately 16 degrees ) that brings important residues into position for catalysis. The potent inhibitor MLN-4760 ((S,S)-2-[1-carboxy-2-[3-(3,5-dichlorobenzyl)-3H-imidazol4-yl]-ethylamino]-4-methylpentanoic acid) makes key binding interactions within the active site and offers insights regarding the action of residues involved in catalysis and substrate specificity. A few active site residue substitutions in ACE2 relative to ACE appear to eliminate the S(2)' substrate-binding subsite and account for the observed reactivity change from the peptidyl dipeptidase activity of ACE to the carboxypeptidase activity of ACE2.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus
Li, W., Moore, M. J., Vasilieva, N., Sui, J., Wong, S. K., Berne, M. A., Somasundaran, M., Sullivan, J. L., Luzuriaga, K., Greenough, T. C., et al. (2003) · Nature · doi:10.1038/nature02145 · Cited by 5,923
Angiotensin-converting enzyme 2 is an essential regulator of heart function
Crackower, M. A., Sarao, R., Oudit, G. Y., Yagil, C., Kozieradzki, I., Scanga, S. E., Oliveira-dos-Santos, A. J., da Costa, J., Zhang, L., Pei, Y., et al. (2002) · Nature · doi:10.1038/nature00786 · Cited by 1,733
Implications of protein flexibility for drug discovery
Teague, S. J. (2003) · Nature Reviews Drug Discovery · doi:10.1038/nrd1129 · Cited by 755
Cited by
Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2
Wang, Q., Zhang, Y., Wu, L., Niu, S., Song, C., Zhang, Z., Lu, G., Qiao, C., Hu, Y., Yuen, K.-Y., et al. (2020) · Cell · doi:10.1016/j.cell.2020.03.045 · Cited by 2,892
“SARS-CoV-2 Applies the CTD to Interact with hACE2 Through bioinformatics analysis, the SARS-CoV-2 S protein has been shown to display characteristic CoV S features, including a S1 region containing the NTD andCTD, S2, a transmembrane region, and a short cytoplasmic domain (Figure S1A).”
InfluentialStructure, Function, and Evolution of Coronavirus Spike Proteins
Li, F. (2016) · Annual Review of Virology · doi:10.1146/annurev-virology-110615-042301 · Cited by 2,740
Severe acute respiratory syndrome coronavirus as an agent of emerging and reemerging infection
Cheng, V. C. C., Lau, S. K. P., Woo, P. C. Y., & Yuen, K. Y. (2007) · Clinical Microbiology Reviews · doi:10.1128/cmr.00023-07 · Cited by 1,192
Hofmann, H., Pyrc, K., van der Hoek, L., Geier, M., Berkhout, B., & Pöhlmann, S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409465102 · Cited by 824
ACE2: from vasopeptidase to SARS virus receptor
Turner, A. J., Hiscox, J. A., & Hooper, N. M. (2004) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2004.04.001 · Cited by 517
Yang, L.-W., & Bahar, I. (2005) · Structure · doi:10.1016/j.str.2005.03.015 · Cited by 273
Devaux, C. A., & Camoin-Jau, L. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.1042200 · Cited by 20
Development and structure-guided characterization of a novel ACE2-binding macrocyclic peptide
Benoit, R. M., Wang, J., Beyer, D., Abbas, A., Rodrigues, M. J., Wieser, M. M., Deupi, X., Müller, C., Suga, H., & Bode, J. W. (2026) · Journal of Structural Biology: X · doi:10.1016/j.yjsbx.2026.100145
Scalable emulation of protein equilibrium ensembles with generative deep learning
Lewis, S., Hempel, T., Jiménez Luna, J., Gastegger, M., Xie, Y., Foong, A. Y. K., García Satorras, V., Abdin, O., Veeling, B. S., Zaporozhets, I., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.05.626885 · Cited by 349
“We show that BioEmu reliably reproduces a stable HEXXH+E motif, the active enzymatic site of this protein [36], with backbone RMSDs below 1.5˚A for all model samples.”
Influential
Metadata
- Authors
- Towler, P., Staker, B., Prasad, S. G., Menon, S., Tang, J., Parsons, T., Ryan, D., Fisher, M., Williams, D., Dales, N. A., Patane, M. A., & Pantoliano, M. W.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2004-04
- Volume
- 279
- Issue
- 17
- Pages
- 17996-18007
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2037650802
- Cited by
- 696
- References
- 3
- FWCI
- 15.83
- Type
- journal article
- Language
- en
- Open access
- hybrid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
