TY - JOUR
T1 - The 3-hydroxy-3-methylglutaryl coenzyme-A reductases from fungi
T2 - A proposal as a therapeutic target and as a study model
AU - Andrade-Pavón, Dulce
AU - Sánchez-Sandoval, Eugenia
AU - Rosales-Acosta, Blanca
AU - Ibarra, José Antonio
AU - Tamariz, Joaquín
AU - Hernández-Rodríguez, César
AU - Villa-Tanaca, Lourdes
N1 - Funding Information:
We would like to thank Cesar I. Ortíz-García for assisting us preparing material for this review. DAP, ESS, and BRA, are CONACyT fellowships, DAP is PIFI fellowship, and grants from CONACyT 133695 and SIP-IPN-20131171 were received. JT, CHR and LVT are EDI and COFAA fellowships. JAI was hired by program “Contratación de investigadores para el apoyo a la investigación y posgrado-IPN”.
PY - 2014/1
Y1 - 2014/1
N2 - The enzyme 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMGR) catalyzes the conversion of HMG-Co-A into mevalonate. This step is the limiting point for the synthesis of cholesterol in mammals and ergosterol in fungi. We describe in this article the genome organization of HMGR coding genes and those deduced from different fungi, recount the evidence showing statins as HMGR inhibitors for ergosterol synthesis and its effect in yeast viability, and propose fungal HMGR (HMGRf) as a model to study the use of pharmaceutical compounds to inhibit cholesterol and ergosterol synthesis. Bibliographical search and bioinformatic analyses were performed and discussed. HMGRfs belong to the class I with a high homology in the catalytic region. The sterol biosynthetic pathway in humans and fungi share many enzymes in the initial steps (such as the HMGR enzyme), but in the last steps enzymes are different rendering the two final products: cholesterol in mammals and ergosterol in fungi. With regards to inhibitors such as statins and other compounds, these affect also fungal viability. Since HMGR from Schizosaccharomyces pombe and Ustilago maydis are very similar to the human HMGR in the catalytic regions, we propose that fungal enzymes can be used to test inhibitors for a potential use in humans. We consider that HMGRf is a good therapeutic target to design and test new antifungal compounds.This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012).
AB - The enzyme 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMGR) catalyzes the conversion of HMG-Co-A into mevalonate. This step is the limiting point for the synthesis of cholesterol in mammals and ergosterol in fungi. We describe in this article the genome organization of HMGR coding genes and those deduced from different fungi, recount the evidence showing statins as HMGR inhibitors for ergosterol synthesis and its effect in yeast viability, and propose fungal HMGR (HMGRf) as a model to study the use of pharmaceutical compounds to inhibit cholesterol and ergosterol synthesis. Bibliographical search and bioinformatic analyses were performed and discussed. HMGRfs belong to the class I with a high homology in the catalytic region. The sterol biosynthetic pathway in humans and fungi share many enzymes in the initial steps (such as the HMGR enzyme), but in the last steps enzymes are different rendering the two final products: cholesterol in mammals and ergosterol in fungi. With regards to inhibitors such as statins and other compounds, these affect also fungal viability. Since HMGR from Schizosaccharomyces pombe and Ustilago maydis are very similar to the human HMGR in the catalytic regions, we propose that fungal enzymes can be used to test inhibitors for a potential use in humans. We consider that HMGRf is a good therapeutic target to design and test new antifungal compounds.This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012).
KW - 3-Hydroxy-3-methylglutaryl coenzyme
KW - A reductase(EC 1.1.1.34)
KW - Ergosterol synthesis
UR - http://www.scopus.com/inward/record.url?scp=84893718650&partnerID=8YFLogxK
U2 - 10.1016/j.riam.2013.10.004
DO - 10.1016/j.riam.2013.10.004
M3 - Estudio breve
C2 - 24270073
SN - 1130-1406
VL - 31
SP - 81
EP - 85
JO - Revista Iberoamericana de Micologia
JF - Revista Iberoamericana de Micologia
IS - 1
ER -