FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2593392007> ?p ?o ?g. }

• W2593392007 endingPage "7243" @default.
• W2593392007 startingPage "7233" @default.
• W2593392007 abstract "Pyrroline-5-carboxylate reductase (PYCR) is the final enzyme in proline biosynthesis, catalyzing the NAD(P)H-dependent reduction of Δ1-pyrroline-5-carboxylate (P5C) to proline. Mutations in the PYCR1 gene alter mitochondrial function and cause the connective tissue disorder cutis laxa. Furthermore, PYCR1 is overexpressed in multiple cancers, and the PYCR1 knock-out suppresses tumorigenic growth, suggesting that PYCR1 is a potential cancer target. However, inhibitor development has been stymied by limited mechanistic details for the enzyme, particularly in light of a previous crystallographic study that placed the cofactor-binding site in the C-terminal domain rather than the anticipated Rossmann fold of the N-terminal domain. To fill this gap, we report crystallographic, sedimentation-velocity, and kinetics data for human PYCR1. Structures of binary complexes of PYCR1 with NADPH or proline determined at 1.9 A resolution provide insight into cofactor and substrate recognition. We see NADPH bound to the Rossmann fold, over 25 A from the previously proposed site. The 1.85 A resolution structure of a ternary complex containing NADPH and a P5C/proline analog provides a model of the Michaelis complex formed during hydride transfer. Sedimentation velocity shows that PYCR1 forms a concentration-dependent decamer in solution, consistent with the pentamer-of-dimers assembly seen crystallographically. Kinetic and mutational analysis confirmed several features seen in the crystal structure, including the importance of a hydrogen bond between Thr-238 and the substrate as well as limited cofactor discrimination." @default.
• W2593392007 created "2017-03-16" @default.
• W2593392007 creator A5008162458 @default.
• W2593392007 creator A5017456472 @default.
• W2593392007 creator A5018030650 @default.
• W2593392007 creator A5021840577 @default.
• W2593392007 creator A5023661618 @default.
• W2593392007 creator A5041507015 @default.
• W2593392007 creator A5071349033 @default.
• W2593392007 date "2017-04-01" @default.
• W2593392007 modified "2023-10-12" @default.
• W2593392007 title "Resolving the cofactor-binding site in the proline biosynthetic enzyme human pyrroline-5-carboxylate reductase 1" @default.
• W2593392007 cites W1578131093 @default.
• W2593392007 cites W1654507542 @default.
• W2593392007 cites W1924684406 @default.
• W2593392007 cites W1967662844 @default.
• W2593392007 cites W1975317507 @default.
• W2593392007 cites W1994052145 @default.
• W2593392007 cites W2003952807 @default.
• W2593392007 cites W2005909918 @default.
• W2593392007 cites W2008162817 @default.
• W2593392007 cites W2011355361 @default.
• W2593392007 cites W2014694459 @default.
• W2593392007 cites W2017178728 @default.
• W2593392007 cites W2033799632 @default.
• W2593392007 cites W2035503835 @default.
• W2593392007 cites W2045143226 @default.
• W2593392007 cites W2059270218 @default.
• W2593392007 cites W2059834438 @default.
• W2593392007 cites W2059890422 @default.
• W2593392007 cites W2061608860 @default.
• W2593392007 cites W2063731290 @default.
• W2593392007 cites W2065929501 @default.
• W2593392007 cites W2075393035 @default.
• W2593392007 cites W2077021664 @default.
• W2593392007 cites W2082150248 @default.
• W2593392007 cites W2090536921 @default.
• W2593392007 cites W2103304356 @default.
• W2593392007 cites W2105406990 @default.
• W2593392007 cites W2109831966 @default.
• W2593392007 cites W2110808180 @default.
• W2593392007 cites W2114773070 @default.
• W2593392007 cites W2124026197 @default.
• W2593392007 cites W2124266141 @default.
• W2593392007 cites W2125934521 @default.
• W2593392007 cites W2131639373 @default.
• W2593392007 cites W2133872445 @default.
• W2593392007 cites W2154197653 @default.
• W2593392007 cites W2154714625 @default.
• W2593392007 cites W2163341755 @default.
• W2593392007 cites W2168735777 @default.
• W2593392007 cites W2180551190 @default.
• W2593392007 cites W2205461107 @default.
• W2593392007 cites W2263732114 @default.
• W2593392007 cites W2269059522 @default.
• W2593392007 cites W2276117228 @default.
• W2593392007 cites W2518402929 @default.
• W2593392007 cites W2525687297 @default.
• W2593392007 cites W2576116195 @default.
• W2593392007 cites W4248872320 @default.
• W2593392007 cites W75870934 @default.
• W2593392007 doi "https://doi.org/10.1074/jbc.m117.780288" @default.
• W2593392007 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5409489" @default.
• W2593392007 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28258219" @default.
• W2593392007 hasPublicationYear "2017" @default.
• W2593392007 type Work @default.
• W2593392007 sameAs 2593392007 @default.
• W2593392007 citedByCount "40" @default.
• W2593392007 countsByYear W25933920072017 @default.
• W2593392007 countsByYear W25933920072018 @default.
• W2593392007 countsByYear W25933920072019 @default.
• W2593392007 countsByYear W25933920072020 @default.
• W2593392007 countsByYear W25933920072021 @default.
• W2593392007 countsByYear W25933920072022 @default.
• W2593392007 countsByYear W25933920072023 @default.
• W2593392007 crossrefType "journal-article" @default.
• W2593392007 hasAuthorship W2593392007A5008162458 @default.
• W2593392007 hasAuthorship W2593392007A5017456472 @default.
• W2593392007 hasAuthorship W2593392007A5018030650 @default.
• W2593392007 hasAuthorship W2593392007A5021840577 @default.
• W2593392007 hasAuthorship W2593392007A5023661618 @default.
• W2593392007 hasAuthorship W2593392007A5041507015 @default.
• W2593392007 hasAuthorship W2593392007A5071349033 @default.
• W2593392007 hasBestOaLocation W25933920071 @default.
• W2593392007 hasConcept C134651460 @default.
• W2593392007 hasConcept C181199279 @default.
• W2593392007 hasConcept C185592680 @default.
• W2593392007 hasConcept C197957613 @default.
• W2593392007 hasConcept C2776977394 @default.
• W2593392007 hasConcept C2779815552 @default.
• W2593392007 hasConcept C515207424 @default.
• W2593392007 hasConcept C55493867 @default.
• W2593392007 hasConcept C71240020 @default.
• W2593392007 hasConceptScore W2593392007C134651460 @default.
• W2593392007 hasConceptScore W2593392007C181199279 @default.
• W2593392007 hasConceptScore W2593392007C185592680 @default.
• W2593392007 hasConceptScore W2593392007C197957613 @default.
• W2593392007 hasConceptScore W2593392007C2776977394 @default.

• next