Structural and biochemical characterisation of Co2+-binding sites on serum albumins and their interplay with fatty acids
Serum albumin–Co2+ interactions are of clinical importance. They play a role in mediating the physiological effects associated with cobalt toxicity and are central to the albumin cobalt binding (ACB) assay for diagnosis of myocardial ischemia. To further understand these processes, a deeper understa...
Saved in:
Published in | Chemical science (Cambridge) Vol. 14; no. 23; pp. 6244 - 6258 |
---|---|
Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Cambridge
Royal Society of Chemistry
14.06.2023
The Royal Society of Chemistry |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Abstract | Serum albumin–Co2+ interactions are of clinical importance. They play a role in mediating the physiological effects associated with cobalt toxicity and are central to the albumin cobalt binding (ACB) assay for diagnosis of myocardial ischemia. To further understand these processes, a deeper understanding of albumin–Co2+ interactions is required. Here, we present the first crystallographic structures of human serum albumin (HSA; three structures) and equine serum albumin (ESA; one structure) in complex with Co2+. Amongst a total of sixteen sites bearing a cobalt ion across the structures, two locations were prominent, and they relate to metal-binding sites A and B. Site-directed mutagenesis and isothermal titration calorimetry (ITC) were employed to characterise sites on HSA. The results indicate that His9 and His67 contribute to the primary (putatively corresponding to site B) and secondary Co2+-binding sites (site A), respectively. The presence of additional multiple weak-affinity Co2+ binding sites on HSA was also supported by ITC studies. Furthermore, addition of 5 molar equivalents of the non-esterified fatty acid palmitate (C16:0) reduced the Co2+-binding affinity at both sites A and B. The presence of bound myristate (C14:0) in the HSA crystal structures provided insight into the fatty acid-mediated structural changes that diminish the affinity of the protein toward Co2+. Together, these data provide further support for the idea that ischemia-modified albumin corresponds to albumin with excessive fatty-acid loading. Collectively, our findings provide a comprehensive understanding of the molecular underpinnings governing Co2+ binding to serum albumin. |
---|---|
AbstractList | Serum albumin–Co2+ interactions are of clinical importance. They play a role in mediating the physiological effects associated with cobalt toxicity and are central to the albumin cobalt binding (ACB) assay for diagnosis of myocardial ischemia. To further understand these processes, a deeper understanding of albumin–Co2+ interactions is required. Here, we present the first crystallographic structures of human serum albumin (HSA; three structures) and equine serum albumin (ESA; one structure) in complex with Co2+. Amongst a total of sixteen sites bearing a cobalt ion across the structures, two locations were prominent, and they relate to metal-binding sites A and B. Site-directed mutagenesis and isothermal titration calorimetry (ITC) were employed to characterise sites on HSA. The results indicate that His9 and His67 contribute to the primary (putatively corresponding to site B) and secondary Co2+-binding sites (site A), respectively. The presence of additional multiple weak-affinity Co2+ binding sites on HSA was also supported by ITC studies. Furthermore, addition of 5 molar equivalents of the non-esterified fatty acid palmitate (C16:0) reduced the Co2+-binding affinity at both sites A and B. The presence of bound myristate (C14:0) in the HSA crystal structures provided insight into the fatty acid-mediated structural changes that diminish the affinity of the protein toward Co2+. Together, these data provide further support for the idea that ischemia-modified albumin corresponds to albumin with excessive fatty-acid loading. Collectively, our findings provide a comprehensive understanding of the molecular underpinnings governing Co2+ binding to serum albumin. Serum albumin–Co 2+ interactions are of clinical importance. They play a role in mediating the physiological effects associated with cobalt toxicity and are central to the albumin cobalt binding (ACB) assay for diagnosis of myocardial ischemia. To further understand these processes, a deeper understanding of albumin–Co 2+ interactions is required. Here, we present the first crystallographic structures of human serum albumin (HSA; three structures) and equine serum albumin (ESA; one structure) in complex with Co 2+ . Amongst a total of sixteen sites bearing a cobalt ion across the structures, two locations were prominent, and they relate to metal-binding sites A and B. Site-directed mutagenesis and isothermal titration calorimetry (ITC) were employed to characterise sites on HSA. The results indicate that His9 and His67 contribute to the primary (putatively corresponding to site B) and secondary Co 2+ -binding sites (site A), respectively. The presence of additional multiple weak-affinity Co 2+ binding sites on HSA was also supported by ITC studies. Furthermore, addition of 5 molar equivalents of the non-esterified fatty acid palmitate (C16:0) reduced the Co 2+ -binding affinity at both sites A and B. The presence of bound myristate (C14:0) in the HSA crystal structures provided insight into the fatty acid-mediated structural changes that diminish the affinity of the protein toward Co 2+ . Together, these data provide further support for the idea that ischemia-modified albumin corresponds to albumin with excessive fatty-acid loading. Collectively, our findings provide a comprehensive understanding of the molecular underpinnings governing Co 2+ binding to serum albumin. Serum albumin–Co 2+ interactions are of clinical importance. |
Author | Shabalin, Ivan G Arya, Swati Schwarz-Linek, Ulrich Czub, Mateusz P Blindauer, Claudia A Wu, Dongmei Stewart, Alan J Fritzen, Remi Minor, Wladek Cooper, David R Gucwa, Michal |
Author_xml | – sequence: 1 givenname: Dongmei surname: Wu fullname: Wu, Dongmei – sequence: 2 givenname: Michal surname: Gucwa fullname: Gucwa, Michal – sequence: 3 givenname: Mateusz surname: Czub middlename: P fullname: Czub, Mateusz P – sequence: 4 givenname: David surname: Cooper middlename: R fullname: Cooper, David R – sequence: 5 givenname: Ivan surname: Shabalin middlename: G fullname: Shabalin, Ivan G – sequence: 6 givenname: Remi surname: Fritzen fullname: Fritzen, Remi – sequence: 7 givenname: Swati surname: Arya fullname: Arya, Swati – sequence: 8 givenname: Ulrich surname: Schwarz-Linek fullname: Schwarz-Linek, Ulrich – sequence: 9 givenname: Claudia surname: Blindauer middlename: A fullname: Blindauer, Claudia A – sequence: 10 givenname: Wladek surname: Minor fullname: Minor, Wladek – sequence: 11 givenname: Alan surname: Stewart middlename: J fullname: Stewart, Alan J |
BookMark | eNpdj0tLxDAQx4MoqKsXP0HAiyDVNK9uTyKLLxA8qOeSx3QbbZM1SdX99tYHgs5lZvj_5gezizZ98IDQQUlOSsLqU8uSIWVF2fMG2qGEl4UUrN78nSnZRvspPZGpGCsFrXbQ-32Oo8ljVD1W3mLtgulgcGbaTaeiMhmiSyq74HFo8SLQ40I7b51f4uQyJDwFCeI4YNXrcXA-fYlyBy5i56fzVa_W-M3lDrcq5zVWxtm0h7Za1SfY_-kz9Hh58bC4Lm7vrm4W57fFirJ5LlpCtSZS1tLOCVS8bblqpa001SChLTnUFaGVpZZLmFhba8FVVQpZC66BsRk6-_auRj2ANeDz9Guzim5Qcd0E5Zq_iXddswyvTUmolJx_Go5-DDG8jJByM7hkoO-VhzCmhs5pRYWcCzmhh__QpzBGP_33SQlBasIo-wDSkYd7 |
ContentType | Journal Article |
Copyright | Copyright Royal Society of Chemistry 2023 This journal is © The Royal Society of Chemistry 2023 The Royal Society of Chemistry |
Copyright_xml | – notice: Copyright Royal Society of Chemistry 2023 – notice: This journal is © The Royal Society of Chemistry 2023 The Royal Society of Chemistry |
DBID | 7SR 8BQ 8FD JG9 7X8 5PM |
DOI | 10.1039/d3sc01723k |
DatabaseName | Engineered Materials Abstracts METADEX Technology Research Database Materials Research Database MEDLINE - Academic PubMed Central (Full Participant titles) |
DatabaseTitle | Materials Research Database Engineered Materials Abstracts Technology Research Database METADEX MEDLINE - Academic |
DatabaseTitleList | Materials Research Database |
DeliveryMethod | fulltext_linktorsrc |
Discipline | Chemistry |
EISSN | 2041-6539 |
EndPage | 6258 |
GrantInformation_xml | – fundername: ; grantid: R01-GM132595 – fundername: ; grantid: RPG-2017-214 – fundername: ; grantid: BB/V014684/1 |
GroupedDBID | -JG 0-7 0R~ 53G 705 7SR 7~J 8BQ 8FD AAEMU AAFWJ AAIWI AAJAE AARTK AAXHV ABEMK ABPDG ABXOH ACGFS ACIWK ADBBV ADMRA AEFDR AENEX AESAV AFLYV AGEGJ AGRSR AGSTE AHGCF AKBGW ALMA_UNASSIGNED_HOLDINGS ANUXI AOIJS APEMP AUDPV AZFZN BCNDV BLAPV BSQNT C6K D0L EE0 EF- F5P GROUPED_DOAJ H13 HYE HZ~ H~N JG9 O-G O9- OK1 PGMZT R7C R7D RAOCF RCNCU RNS RPM RRC RSCEA RVUXY SKA SKF SKH SKJ SKM SKR SKZ SLC SLF SLH SMJ 7X8 5PM AFPKN |
ID | FETCH-LOGICAL-p238t-f02bb06696d80e74ff4af6d7b2be6ef14e97027d2d46e02bd9b54a7156954be33 |
IEDL.DBID | RPM |
ISSN | 2041-6520 |
IngestDate | Tue Sep 17 21:30:05 EDT 2024 Fri Oct 25 03:55:46 EDT 2024 Thu Oct 10 19:57:39 EDT 2024 |
IsDoiOpenAccess | true |
IsOpenAccess | true |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 23 |
Language | English |
LinkModel | DirectLink |
MergedId | FETCHMERGED-LOGICAL-p238t-f02bb06696d80e74ff4af6d7b2be6ef14e97027d2d46e02bd9b54a7156954be33 |
Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Present address: Laboratory of Biomolecular Research, Paul Scherrer Institute, Villigen, Switzerland. These authors contributed equally to the work. |
OpenAccessLink | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10266443/ |
PQID | 2825509032 |
PQPubID | 2047492 |
PageCount | 15 |
ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_10266443 proquest_miscellaneous_2827256856 proquest_journals_2825509032 |
PublicationCentury | 2000 |
PublicationDate | 2023-06-14 |
PublicationDateYYYYMMDD | 2023-06-14 |
PublicationDate_xml | – month: 06 year: 2023 text: 2023-06-14 day: 14 |
PublicationDecade | 2020 |
PublicationPlace | Cambridge |
PublicationPlace_xml | – name: Cambridge |
PublicationTitle | Chemical science (Cambridge) |
PublicationYear | 2023 |
Publisher | Royal Society of Chemistry The Royal Society of Chemistry |
Publisher_xml | – name: Royal Society of Chemistry – name: The Royal Society of Chemistry |
SSID | ssj0000331527 |
Score | 2.4834385 |
Snippet | Serum albumin–Co2+ interactions are of clinical importance. They play a role in mediating the physiological effects associated with cobalt toxicity and are... Serum albumin–Co 2+ interactions are of clinical importance. They play a role in mediating the physiological effects associated with cobalt toxicity and are... |
SourceID | pubmedcentral proquest |
SourceType | Open Access Repository Aggregation Database |
StartPage | 6244 |
SubjectTerms | Affinity Binding sites Chemistry Cobalt Crystal structure Crystallography Esterification Fatty acids Ischemia Physiological effects Serum albumin Structural analysis Titration calorimetry Toxicity |
Title | Structural and biochemical characterisation of Co2+-binding sites on serum albumins and their interplay with fatty acids |
URI | https://www.proquest.com/docview/2825509032 https://search.proquest.com/docview/2827256856 https://pubmed.ncbi.nlm.nih.gov/PMC10266443 |
Volume | 14 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3fS8MwEA5zL_oi_sTpHBF8k65tkqbtowzHEBRBB3srSZNicWsH7cD9916yVtdXny9py-Xo3eW--w6hezhSJk3rlvRT6jDfk45UhnLftOsyT1ClLdvnK5_N2fMiWPQQb3thLGg_lfm4WK7GRf5psZXrVeq2ODH37WUCTpGDH6fuAToA_7uXo9v_L6XNrFZ4m-_wgHgtLymNXUWr1OQ99KsTU3YRkXsuZnqCjpvYED_uvuEU9XRxhg4n7Ui2c_T9btleDVMGFoXCMjfzrmzDP07_mJetsnGZ4UlJHkzqa_wTNmXiCoMAjG6zwhaXnBeVfZAtF-DcAhCXYovN7SzORF1vsUhzVV2g-fTpYzJzmtEJzhp8cO1kHpESoomYq8jTIcsyJjKuQkmk5jrzmY5DSEgVUYxrWKtiGTARQjIXB0xqSi9RvygLfYUwBASKS0Vi6SlGWSgYCTns9mRKUhFGAzRs1Zg09l8lpiM2MFdAZIDufsWgLVOOEIUuN3ZNCAFXFPABijrqT9Y7po3EcF93JWASlgO7NYHr_2-9QUdmdrzBfflsiPpwgvoWIoxajmxmPrJm9QMggdZD |
link.rule.ids | 230,314,727,780,784,864,885,27924,27925,53791,53793 |
linkProvider | National Library of Medicine |
linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1LT8MwDLbGOIwL4inGM0jcULc2SZP1iCbQgIGQGBK3KmlSUcG6SR0S_HucbIXtyjmPVo5b2_HnzwAXeKRcu9ItHWUs4FGoA20c5b4r1-WhYsZ6ts9HMXjhd6_xawNEXQvjQfuZLjrlx7hTFm8eWzkdZ90aJ9Z9euijURRox1l3DdZjJpNoKUr3f2DGFt1a8XlRIGIa1sykLOkaVmUu8mHvK17lKiZyycjcbMHmwjskV_O32IaGLXeg1a-bsu3C17Pne3VcGUSVhujCdbzyJf8k--Ne9uImk5z0J_TSBb_OQhGXKK4IDqDafY6JRyYXZeU38gkDUngI4of6Ju5-luRqNvsmKitMtQcvN9ej_iBYNE8IpmiFZ0EeUq3Rn0iE6YVW8jznKhdGaqqtsHnEbSIxJDXUcGFxrkl0zJXEcC6JubaM7UOznJT2AAi6BEZoQxMdGs64VJxKgatDndFMyV4bjmsxposvoEpdTWzsLoFoG85_h1FaLiGhSjv59HMkuly9WLShtyL-dDrn2kgd-_XqCCqFZ8GuleDw_0vPoDUYPQzT4e3j_RFsuE7yDgUW8WNo4mnaE_Q3ZvrUK9cPfGrYow |
linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1LS8QwEA4-QL2IT1yfEbxJbZukaXuU6rI-WVDBW0maFItuutAV3H_vJLa6e_WcR8tk2pnJfPMNQmdwpEza0i0ZFtRjYSA9qSzlvi3XZYGgSju2z0c-eGG3r9Fri6psWlilKWR1YT5GF6Z6c9jK8ajwO5yYP3zIwChysOPUH6vSX0TLEQUtm4nU3V-Y0rZjKzwz9HhEgo6dlKa-ok1hox_6PudZzuMiZwxNfwOttx4ivvx5k020oM0WWs26xmzb6OvJcb5avgwsjMKysl2vXNk_Lv74l53IcV3irCbnNgC2VgrbZHGDYQBU73OEHTq5Mo3byCUNcOVgiB9iiu0dLS7FZDLFoqhUs4Ne-tfP2cBrGyh4Y7DEE68MiJTgU6RcJYGOWVkyUXIVSyI112XIdBpDWKqIYlzDXJXKiIkYQro0YlJTuouWTG30HsLgFiguFUlloBhlsWAk5rA6kAUpRJz00GEnxrz9Cprc1sVG9iKI9NDp7zBIyyYlhNH1p5sTg9uVRLyHkjnx5-Mfvo3cMmDPj4BiOCbsThH2_7_0BK0Mr_r5_c3j3QFas83kLRAsZIdoCQ5TH4HLMZHHTre-AZH52bY |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Structural+and+biochemical+characterisation+of+Co2%2B-binding+sites+on+serum+albumins+and+their+interplay+with+fatty+acids&rft.jtitle=Chemical+science+%28Cambridge%29&rft.au=Wu%2C+Dongmei&rft.au=Gucwa%2C+Michal&rft.au=Czub%2C+Mateusz+P&rft.au=Cooper%2C+David+R&rft.date=2023-06-14&rft.pub=Royal+Society+of+Chemistry&rft.issn=2041-6520&rft.eissn=2041-6539&rft.volume=14&rft.issue=23&rft.spage=6244&rft.epage=6258&rft_id=info:doi/10.1039%2Fd3sc01723k&rft.externalDBID=NO_FULL_TEXT |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2041-6520&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2041-6520&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2041-6520&client=summon |