4x92 › Citations

Structure and function of lysosomal phospholipase A2 and lecithin:cholesterol acyltransferase.

Figure 1
Figure 2
Figure 3
Glukhova A, Hinkovska-Galcheva V, Kelly R, Abe A, Shayman JA, Tesmer JJ
OpenAccess logo Nat Commun 6 6250 (2015)
Related entries: 4x90, 4x91, 4x93, 4x94, 4x95, 4x96, 4x97

Cited: 48 times
EuropePMC logo PMID: 25727495

Abstract

Lysosomal phospholipase A2 (LPLA2) and lecithin:cholesterol acyltransferase (LCAT) belong to a structurally uncharacterized family of key lipid-metabolizing enzymes responsible for lung surfactant catabolism and for reverse cholesterol transport, respectively. Whereas LPLA2 is predicted to underlie the development of drug-induced phospholipidosis, somatic mutations in LCAT cause fish eye disease and familial LCAT deficiency. Here we describe several high-resolution crystal structures of human LPLA2 and a low-resolution structure of LCAT that confirms its close structural relationship to LPLA2. Insertions in the α/β hydrolase core of LPLA2 form domains that are responsible for membrane interaction and binding the acyl chains and head groups of phospholipid substrates. The LCAT structure suggests the molecular basis underlying human disease for most of the known LCAT missense mutations, and paves the way for rational development of new therapeutics to treat LCAT deficiency, atherosclerosis and acute coronary syndrome.

Reviews - 4x92 mentioned but not cited (1)

  1. Carboxylic ester hydrolases: Classification and database derived from their primary, secondary, and tertiary structures. Chen Y, Black DS, Reilly PJ. Protein Sci 25 1942-1953 (2016)

Articles - 4x92 mentioned but not cited (1)

  1. Structure and function of lysosomal phospholipase A2 and lecithin:cholesterol acyltransferase. Glukhova A, Hinkovska-Galcheva V, Kelly R, Abe A, Shayman JA, Tesmer JJ. Nat Commun 6 6250 (2015)


Reviews citing this publication (5)

  1. Lysosomal phospholipase A2. Shayman JA, Tesmer JJG. Biochim Biophys Acta Mol Cell Biol Lipids 1864 932-940 (2019)
  2. Properties and Biotechnological Applications of Acyl-CoA:diacylglycerol Acyltransferase and Phospholipid:diacylglycerol Acyltransferase from Terrestrial Plants and Microalgae. Xu Y, Caldo KMP, Pal-Nath D, Ozga J, Lemieux MJ, Weselake RJ, Chen G. Lipids 53 663-688 (2018)
  3. Inhibition of lysosomal phospholipase A2 predicts drug-induced phospholipidosis. Hinkovska-Galcheva V, Treadwell T, Shillingford JM, Lee A, Abe A, Tesmer JJG, Shayman JA. J Lipid Res 62 100089 (2021)
  4. Relationships of human α/β hydrolase fold proteins and other organophosphate-interacting proteins. Lenfant N, Bourne Y, Marchot P, Chatonnet A. Chem Biol Interact 259 343-351 (2016)
  5. Targeting host-specific metabolic pathways-opportunities and challenges for anti-infective therapy. Konaklieva MI, Plotkin BJ. Front Mol Biosci 11 1338567 (2024)

Articles citing this publication (41)

  1. CASTp 3.0: computed atlas of surface topography of proteins. Tian W, Chen C, Lei X, Zhao J, Liang J. Nucleic Acids Res 46 W363-W367 (2018)
  2. How the Same Core Catalytic Machinery Catalyzes 17 Different Reactions: the Serine-Histidine-Aspartate Catalytic Triad of α/β-Hydrolase Fold Enzymes. Rauwerdink A, Kazlauskas RJ. ACS Catal 5 6153-6176 (2015)
  3. Solution structure of discoidal high-density lipoprotein particles with a shortened apolipoprotein A-I. Bibow S, Polyhach Y, Eichmann C, Chi CN, Kowal J, Albiez S, McLeod RA, Stahlberg H, Jeschke G, Güntert P, Riek R. Nat Struct Mol Biol 24 187-193 (2017)
  4. Lipoprotein X Causes Renal Disease in LCAT Deficiency. Ossoli A, Neufeld EB, Thacker SG, Vaisman B, Pryor M, Freeman LA, Brantner CA, Baranova I, Francone NO, Demosky SJ, Vitali C, Locatelli M, Abbate M, Zoja C, Franceschini G, Calabresi L, Remaley AT. PLoS One 11 e0150083 (2016)
  5. A Lipolytic Lecithin:Cholesterol Acyltransferase Secreted by Toxoplasma Facilitates Parasite Replication and Egress. Pszenny V, Ehrenman K, Romano JD, Kennard A, Schultz A, Roos DS, Grigg ME, Carruthers VB, Coppens I. J Biol Chem 291 3725-3746 (2016)
  6. The high-resolution crystal structure of human LCAT. Piper DE, Romanow WG, Gunawardane RN, Fordstrom P, Masterman S, Pan O, Thibault ST, Zhang R, Meininger D, Schwarz M, Wang Z, King C, Zhou M, Walker NP. J Lipid Res 56 1711-1719 (2015)
  7. A retractable lid in lecithin:cholesterol acyltransferase provides a structural mechanism for activation by apolipoprotein A-I. Manthei KA, Ahn J, Glukhova A, Yuan W, Larkin C, Manett TD, Chang L, Shayman JA, Axley MJ, Schwendeman A, Tesmer JJG. J Biol Chem 292 20313-20327 (2017)
  8. Lecithin:Cholesterol Acyltransferase Activation by Sulfhydryl-Reactive Small Molecules: Role of Cysteine-31. Freeman LA, Demosky SJ, Konaklieva M, Kuskovsky R, Aponte A, Ossoli AF, Gordon SM, Koby RF, Manthei KA, Shen M, Vaisman BL, Shamburek RD, Jadhav A, Calabresi L, Gucek M, Tesmer JJG, Levine RL, Remaley AT. J Pharmacol Exp Ther 362 306-318 (2017)
  9. Molecular basis for activation of lecithin:cholesterol acyltransferase by a compound that increases HDL cholesterol. Manthei KA, Yang SM, Baljinnyam B, Chang L, Glukhova A, Yuan W, Freeman LA, Maloney DJ, Schwendeman A, Remaley AT, Jadhav A, Tesmer JJ. Elife 7 e41604 (2018)
  10. Structural analysis of lecithin:cholesterol acyltransferase bound to high density lipoprotein particles. Manthei KA, Patra D, Wilson CJ, Fawaz MV, Piersimoni L, Shenkar JC, Yuan W, Andrews PC, Engen JR, Schwendeman A, Ohi MD, Tesmer JJG. Commun Biol 3 28 (2020)
  11. Congress Lecithin:cholesterol acyltransferase: symposium on 50 years of biomedical research from its discovery to latest findings. Norum KR, Remaley AT, Miettinen HE, Strøm EH, Balbo BEP, Sampaio CATL, Wiig I, Kuivenhoven JA, Calabresi L, Tesmer JJ, Zhou M, Ng DS, Skeie B, Karathanasis SK, Manthei KA, Retterstøl K. J Lipid Res 61 1142-1149 (2020)
  12. Novel lecithin: cholesterol acyltransferase-based therapeutic approaches. Freeman LA, Karathanasis SK, Remaley AT. Curr Opin Lipidol 31 71-79 (2020)
  13. Preferential hydrolysis of truncated oxidized glycerophospholipids by lysosomal phospholipase A2. Abe A, Hiraoka M, Ohguro H, Tesmer JJ, Shayman JA. J Lipid Res 58 339-349 (2017)
  14. Interaction of lecithin:cholesterol acyltransferase with lipid surfaces and apolipoprotein A-I-derived peptides. Casteleijn MG, Parkkila P, Viitala T, Koivuniemi A. J Lipid Res 59 670-683 (2018)
  15. Metabolomics Study of the Biochemical Changes in the Plasma of Myocardial Infarction Patients. Zhu M, Han Y, Zhang Y, Zhang S, Wei C, Cong Z, Du W. Front Physiol 9 1017 (2018)
  16. Lysosome-Dependent LXR and PPARδ Activation Upon Efferocytosis in Human Macrophages. Mota AC, Dominguez M, Weigert A, Snodgrass RG, Namgaladze D, Brüne B. Front Immunol 12 637778 (2021)
  17. Proteomic and lipidomic profiling of demyelinating lesions identifies fatty acids as modulators in lesion recovery. Penkert H, Bertrand A, Tiwari V, Breimann S, Müller SA, Jordan PM, Gerl MJ, Klose C, Cantuti-Castelvetri L, Bosch-Queralt M, Levental I, Lichtenthaler SF, Werz O, Simons M. Cell Rep 37 109898 (2021)
  18. Intramolecular electrostatic interactions contribute to phospholipase Cβ3 autoinhibition. Esquina CM, Garland-Kuntz EE, Goldfarb D, McDonald EK, Hudson BN, Lyon AM. Cell Signal 62 109349 (2019)
  19. Direct observation of conformational dynamics of the PH domain in phospholipases Cϵ and β may contribute to subfamily-specific roles in regulation. Garland-Kuntz EE, Vago FS, Sieng M, Van Camp M, Chakravarthy S, Blaine A, Corpstein C, Jiang W, Lyon AM. J Biol Chem 293 17477-17490 (2018)
  20. Development of a novel fluorescent activity assay for lecithin:cholesterol acyltransferase. Sakurai T, Sakurai A, Vaisman BL, Nishida T, Neufeld EB, Demosky SJ, Sampson ML, Shamburek RD, Freeman LA, Remaley AT. Ann Clin Biochem 55 414-421 (2018)
  21. Insights into ultra-low affinity lipase-antibody noncovalent complex binding mechanisms. Hecht ES, Mehta S, Wecksler AT, Aguilar B, Swanson N, Phung W, Dubey Kelsoe A, Benner WH, Tesar D, Kelley RF, Sandoval W, Sreedhara A. MAbs 14 2135183 (2022)
  22. rHDL modeling and the anchoring mechanism of LCAT activation. Laurenzi T, Parravicini C, Palazzolo L, Guerrini U, Gianazza E, Calabresi L, Eberini I. J Lipid Res 62 100006 (2021)
  23. Determinants of pH profile and acyl chain selectivity in lysosomal phospholipase A2. Hinkovska-Galcheva V, Kelly R, Manthei KA, Bouley R, Yuan W, Schwendeman A, Tesmer JJG, Shayman JA. J Lipid Res 59 1205-1218 (2018)
  24. M05B5.4 (lysosomal phospholipase A2) promotes disintegration of autophagic vesicles to maintain C. elegans development. Li Y, Wang X, Li M, Yang C, Wang X. Autophagy 18 595-607 (2022)
  25. Genome-Wide CRISPR-Cas9 Screen Does Not Identify Host Factors Modulating Streptococcus agalactiae β-Hemolysin/Cytolysin-Induced Cell Death. Shahi I, Llaneras CN, Perelman SS, Torres VJ, Ratner AJ. Microbiol Spectr 10 e0218621 (2022)
  26. Identification and functional analysis of missense mutations in the lecithin cholesterol acyltransferase gene in a Chilean patient with hypoalphalipoproteinemia. Tobar HE, Cataldo LR, González T, Rodríguez R, Serrano V, Arteaga A, Álvarez-Mercado A, Lagos CF, Vicuña L, Miranda JP, Pereira A, Bravo C, Aguilera CM, Eyheramendy S, Uauy R, Martínez Á, Gil Á, Francone O, Rigotti A, Santos JL. Lipids Health Dis 18 132 (2019)
  27. p-Methoxycinnamic Acid Diesters Lower Dyslipidemia, Liver Oxidative Stress and Toxicity in High-Fat Diet Fed Mice and Human Peripheral Blood Lymphocytes. Paim RTT, Rodrigues PSA, Silva JYGD, Paula Junior VF, Silva BBD, Freitas CAS, Oriá RB, Florean EOPT, Rondina D, Guedes MIF. Nutrients 12 E262 (2020)
  28. Acyl-CoA-dependent and acyl-CoA-independent avocado acyltransferases positively influence oleic acid content in nonseed triacylglycerols. Behera J, Rahman MM, Shockey J, Kilaru A. Front Plant Sci 13 1056582 (2022)
  29. Effect of Short-Chain Fatty Acids and Polyunsaturated Fatty Acids on Metabolites in H460 Lung Cancer Cells. Zhou T, Yang K, Huang J, Fu W, Yan C, Wang Y. Molecules 28 2357 (2023)
  30. Metabolite Patterns in Human Myeloid Hematopoiesis Result from Lineage-Dependent Active Metabolic Pathways. Kaiser L, Weinschrott H, Quint I, Blaess M, Csuk R, Jung M, Kohl M, Deigner HP. Int J Mol Sci 21 E6092 (2020)
  31. Single nucleotide polymorphisms in LCAT may contribute to dyslipidaemia in HIV-infected individuals on HAART in a Ghanaian population. Bani SB, Danquah KO, Obirikorang C, Owiredu WKBA, Quaye L, Muonir Der E, Acheampong E, Adams Y, Dapare PPM, Banyeh M, Anto EO, Sakyi SA. Sci Rep 10 19419 (2020)
  32. Structural Basis of Lysosomal Phospholipase A2 Inhibition by Zn2. Bouley RA, Hinkovska-Galcheva V, Shayman JA, Tesmer JJG. Biochemistry 58 1709-1717 (2019)
  33. Transcriptome Analysis and Identification of Lipid Genes in Physaria lindheimeri, a Genetic Resource for Hydroxy Fatty Acids in Seed Oil. Chen GQ, Kim WN, Johnson K, Park ME, Lee KR, Kim HU. Int J Mol Sci 22 E514 (2021)
  34. Bioinformatic analysis of Chinese hamster ovary host cell protein lipases. MacDonald ML, Hamaker N, Lee KH. AIChE J 64 4247-4254 (2018)
  35. Influence of lecithin cholesterol acyltransferase alteration during different pathophysiologic conditions: A 45 years bibliometrics analysis. Gao H, Wu J, Sun Z, Zhang F, Shi T, Lu K, Qian D, Yin Z, Zhao Y, Qin J, Xue B. Front Pharmacol 13 1062249 (2022)
  36. Cellular Export Fate of Liposomal Spherical Nucleic Acids. Paranandi KS, Lee A, Stanic N, Mirkin CA. ACS Nano 17 19000-19010 (2023)
  37. Case Reports Familial LCAT Deficiency and Low HDL-C Levels: In silico Characterization of Two Rare LCAT Missense Mutations. Ciro Acosta S, Díaz-Ordóñez L, Gutierrez-Medina JD, Silva-Cuero YK, Arango-Vélez LG, García-Trujillo AO, Pachajoa H. Appl Clin Genet 17 23-32 (2024)
  38. Illuminating a biologics development challenge: systematic characterization of CHO cell-derived hydrolases identified in monoclonal antibody formulations. Maier M, Weiß L, Zeh N, Schmieder-Todtenhaupt V, Dehghani A, Felix MN, Heinzelmann D, Lindner B, Schmidt M, Studts J, Schulz P, Reisinger B, Otte K, Franzreb M, Lakatos D, Fischer S. MAbs 16 2375798 (2024)
  39. Rescue of Familial Lecithin:Cholesterol Acyltranferase Deficiency Mutations with an Allosteric Activator. Manthei KA, Tremonti GE, Chang L, Niemelä A, Giorgi L, Koivuniemi A, Tesmer JJG. Mol Pharmacol 106 188-197 (2024)
  40. The role of lysosomal phospholipase A2 in the catabolism of bis(monoacylglycerol)phosphate and association with phospholipidosis. Abe A, Hinkovska-Galcheva V, Bouchev P, Bouley R, Shayman JA. J Lipid Res 65 100574 (2024)
  41. β-Cryptoxanthin-Biofortified Hen Eggs Enhance Vitamin A Status When Fed to Male Mongolian Gerbils. Heying EK, Ziemer KL, Tanumihardjo JP, Palacios-Rojas N, Tanumihardjo SA. J Nutr 148 1236-1243 (2018)


Quick links