{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T05:33:13Z","timestamp":1762061593717,"version":"build-2065373602"},"reference-count":50,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T00:00:00Z","timestamp":1659916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Foundation","award":["DBI 2000296","U100193","IIS 1924092","2U54MD007597"],"award-info":[{"award-number":["DBI 2000296","U100193","IIS 1924092","2U54MD007597"]}]},{"DOI":"10.13039\/100012365","name":"Howard University startup funds","doi-asserted-by":"publisher","award":["DBI 2000296","U100193","IIS 1924092","2U54MD007597"],"award-info":[{"award-number":["DBI 2000296","U100193","IIS 1924092","2U54MD007597"]}],"id":[{"id":"10.13039\/100012365","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Science Foundation","award":["DBI 2000296","U100193","IIS 1924092","2U54MD007597"],"award-info":[{"award-number":["DBI 2000296","U100193","IIS 1924092","2U54MD007597"]}]},{"DOI":"10.13039\/100000002","name":"National Institute on Minority Health and Health Disparities of the National Institutes of Health","doi-asserted-by":"publisher","award":["DBI 2000296","U100193","IIS 1924092","2U54MD007597"],"award-info":[{"award-number":["DBI 2000296","U100193","IIS 1924092","2U54MD007597"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Myeloperoxidase (MPO) is a heme peroxidase with microbicidal properties. MPO plays a role in the host\u2019s innate immunity by producing reactive oxygen species inside the cell against foreign organisms. However, there is little functional evidence linking missense mutations to human diseases. We utilized in silico saturation mutagenesis to generate and analyze the effects of 10,811 potential missense mutations on MPO stability. Our results showed that ~71% of the potential missense mutations destabilize MPO, and ~8% stabilize the MPO protein. We showed that G402W, G402Y, G361W, G402F, and G655Y would have the highest destabilizing effect on MPO. Meanwhile, D264L, G501M, D264H, D264M, and G501L have the highest stabilization effect on the MPO protein. Our computational tool prediction showed the destabilizing effects in 13 out of 14 MPO missense mutations that cause diseases in humans. We also analyzed putative post-translational modification (PTM) sites on the MPO protein and mapped the PTM sites to disease-associated missense mutations for further analysis. Our analysis showed that R327H associated with frontotemporal dementia and R548W causing generalized pustular psoriasis are near these PTM sites. Our results will aid further research into MPO as a biomarker for human complex diseases and a candidate for drug target discovery.<\/jats:p>","DOI":"10.3390\/genes13081412","type":"journal-article","created":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T21:09:18Z","timestamp":1659992958000},"page":"1412","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Prediction of the Effects of Missense Mutations on Human Myeloperoxidase Protein Stability Using In Silico Saturation Mutagenesis"],"prefix":"10.3390","volume":"13","author":[{"given":"Adebiyi","family":"Sobitan","sequence":"first","affiliation":[{"name":"Department of Biology, Howard University, Washington, DC 20059, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Edwards","sequence":"additional","affiliation":[{"name":"Department of Biology, Howard University, Washington, DC 20059, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8084-6724","authenticated-orcid":false,"given":"Md Shah","family":"Jalal","sequence":"additional","affiliation":[{"name":"Department of Biology, Howard University, Washington, DC 20059, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6354-429X","authenticated-orcid":false,"given":"Ayanfeoluwa","family":"Kolawole","sequence":"additional","affiliation":[{"name":"Department of Biology, Howard University, Washington, DC 20059, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1748-3398","authenticated-orcid":false,"given":"Hemayet","family":"Ullah","sequence":"additional","affiliation":[{"name":"Department of Biology, Howard University, Washington, DC 20059, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atanu","family":"Duttaroy","sequence":"additional","affiliation":[{"name":"Department of Biology, Howard University, Washington, DC 20059, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering and Computer Science, Howard University, Washington, DC 20059, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaolei","family":"Teng","sequence":"additional","affiliation":[{"name":"Department of Biology, Howard University, Washington, DC 20059, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.abb.2018.01.004","article-title":"Myeloperoxidase: Its role for host defense, inflammation, and neutrophil function","volume":"Volume 640","author":"Aratani","year":"2018","journal-title":"Archives of Biochemistry and Biophysics"},{"key":"ref_2","first-page":"33","article-title":"Myeloperoxidase as an Active Disease Biomarker: Recent Biochemical and Pathological Perspectives","volume":"6","author":"Khan","year":"2018","journal-title":"Med. 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