phosphoribosyl glycinamide formail transferes

phosphoribosyl glycinamide formail transferes (, "2-amaino-enn-ribosile glycinamide 5 '-fasfate transformylase", "gaar formail transferes", "gaar transformylase", "glycinamide ribonucleotide transformylase", "gaar tifface", "5,10-methanil tetrahydropholate 2-amaino-enn-ribosylcytemide ribonucleotide transformylase") anedi "10-formail tetrahydropholate 5'-phosphoribosyl glycinamide enn-formail transferes" anae kramabaddhamaina paerutoe unde enjaim. eee enjaim eee krindi rasayana praticharyanu utprerakam chestundi
eee thf aadhaarita enjaim paina chuupina vidhamgaa n2-formail-n1 (5-phospho-dii-ribosyl) glycinamide (fgar) nuu roopondinchadaaniki 10-pharmyeltetrahydrophol (fthf) nundi n1-(5-phospho-dii-ribosyl) glycinamide (gar) varaku formill samuuham yokka nucleophilic asil pratyaamnaayaanni utprerakam chestundi. eee praticharya "dii novo" purin jeevasansleshanha maargam dwara purin erpadatamlo mukhyamaina paatra poeshistumdi. eee maargam adenosine monophosphate (amp) mariyu gwanosin monophosphate (zii. emm. pii) laku puurvagaami ayina inosine monophosphate (imp) nuu srushtistundi. ATP, NAD + mariyu fyaad vanti mukhyamaina shakti vahakalu mariyu camp vanti signalling anuvulaku ampere oka building block. dii novo" purin biosynthesislo gartphace paatra dheenini cancer nirodhaka aushadhaalaku lakshyamgaa chestundi mariyu prasavaanantara abhivruddhi samayamlo daani athi vyakteekarana down syndromtho anusandhaaninchabadindi. e loe gaar transformylasenu encoding chese rendu rakaala janyuvulu unnaayi.kolaih purn mariyu purt, ayithe purn matrame maanavulalo kanipistundi. kriyaaseela pradaesamloe aneka avasheshaalu bacteria, eest, avian mariyu maanava enjaimlalo samrakshinchabadataayi.
enjaim nirmaanam.
maanavulalo, gartphace anedi trifunctional enjaimlo bhaagam, indulo glycinamide ribonucleotide synthase (gars) mariyu aminomedazole ribonucleotide synthase (air) kooda untaayi. eee protein (110kda) dii novo purin biosynthesis yokka 2,3 mariyu 5 dasalanu utprerakam chestundi. eee enjaim unitla saameepyata mariyu protein yokka vasyata maargam nirgamaamsaanni penchadaaniki upayogapadutundi. gartphace protein yokka sii-terminal chivaralo untundi.
maanava gartphace aaviri-vyaapti sitting drop paddhati dwara sphatikeekarinchabadindi mariyu stanford synchrotron radiation laboratory (ssrl) vadda kaneesam rendu samuuhaala dwara chithreekarinchabadindi.
edu-stranded beata sheet dwara anusandhaaninchabadina rendu upa domainla dwara nirmaanaanni vivarinchavacchu. enn-terminal domine roseman rakam mononucleotide madatanu kaligi untundi, beata sheet yokka naalugu strand bhaagamtho prati vaipu rendu alfa helix chuttoo untundi. beata sheet sii terminal domainloki konasaagutundi, ikkada oka vaipu idhi podavaina alfa helix thoo kappabadi untundi mariyu marovaipu idhi paakshikamgaa draavakanki guravutundi. idhi kriyaaseela sait unna rendu upa domainla madhya cheelika.
cheelikalo gaar binding sait mariyu folate binding paaket untaayi. folate binding paaket terridine-binding cheelika, formill badilee praantam mariyu benzoilglutamate praantam dwara varninchabadindi, idhi terridine talanu mariyu fthf yokka formill-bound natrajani dwara anusandhaaninchabadina benzoilglutamate thokanu bandhistundi. eee folate binding praantam chaalaa parisoedhanaku sambandhinchinadi endukante chinna anuvula dwara daani nirodham antinoplastic aushadhaala aavishkaranaku daariteesindi. folate binding loop draavanam yokka pihechnu batti conformation maarustundani choopabadindi mariyu maanava gaar transformylase pihech 7.5-8 chuttoo atyadhika kaaryaacharananu chooputundi. takkuva pihech (~ 4.2) paristhitulu uparitalam (gaar) binding loopla conformation kooda maarustaayi.
yantraangam.
purn gartphace yokka yantraangam.
clain mariyu itarulu modata neeti anuvu sahayamtho kuudina yantraamgaanni suuchimchaaru. nirantara modata avasheshaala yokka carboxylate samuuhamtoe hydrogen bandham dwara unchabadina oke neeti anuvu, protaanlanu gaar-enn nundi nundi badilee chestundi. gaar yokka antima amaino samuuhamlooni nucleophilic natrajani formail samuuham yokka carbonyl carbonpy daadi chestundi, idhi oxygennu pratikuula chaarj meeda nettivestundi. clain thana 108 pratikuulamgaa chaarj cheyabadina oxygentho hydrogen bandham dwara parivartana sthithini sthireekaristundani mariyu carbonyl double baand yokka samskarana thf-n-formail baandnu vichchinnam cheyadamlo phalitamavutundani suuchistumdi. khiao mariyu itarula gananalu gaar-enn nundi thf-n kuu neeti sahayamtho dasalavaareegaa protan badilee clain suuchimchina ekikruta badilee kante 80-100 kj/mol marinta anukuulamgaa untundani suuchistunnaayi. chuupina yantraamgaanni kwavo mariyu itarulu suuchimchaaru, vaaru tama lekkalalo chuttupakkala avasheshaalanu parigananaloki teesukoledani angeekaristunnaaru. gaar tifface paie prarambha kriyaaseela sait mapping chaalaa varaku bacteria enjaim thoo nirnayinchabadindi, endukante e loe daani athi vyakteekarana nundi labhinche parimaanam kaaranamgaa. kolai. bromoesityl dideazapholate affinityni upayoginchi analog james inglis mariyu sahacharulu modata modata nuu formill badilee yantraamgamlo palgone kriyaaseela sait avasheshamgaa gurtinchaaru.
purt gartphace yokka yantraangam.
e loe gaar transformylase yokka purt roopaantaram yokka adhyayanalu.eee praticharya formail fasfate madhyantaram dwara konasaagutundani kooli kanugondi. inn vitro praticharya thf lekunda konasaagavacchu, mottam meeda inn vivo praticharya okate.
dii novo" purin biosynthesislo prameyam.
gaart "dii novo" purin biosynthesislo moodava dasanu utprerakam chestundi, n2-formail-n1 (5-phospho-dii-ribosyl) glycinamide (fgr) nuu n1 (5-phospho-dii-ribosyl) glycinamide (gaar) kuu formill adanamgaa erpadutundi. ii loe. kolai, purn enjaim anedi 23 kda protein, conny maanavulalo idhi 110 kda yokka trifunctional proteinlo bhaagam, indulo gaali mariyu gars kaaryaacharanalu untaayi. eee protein "dii novo" purin maargam yokka moodu ververu dasalanu utprerakam chestundi.
vyaadhi yokka praamukhyata.
cancer lakshyam.
vaati perigina perugudala raetu mariyu jeevakriya avasaraala kaaranamgaa, cancer kanaalu avasaramaina ampere mariyu zii. emm. pii sthaayilanu saadhinchadaaniki "dii novo" nucleotide biosynthesis paie aadhaarapadataayi. dii novo" purin maargam yokka yea dasalanu ayina nirodhinchagalagadam kaniti perugudalalo gananeeyamaina taggimpunu andistundi. inhibitarlanu kanugonadaaniki uparitala bandham mariyu folate bandham sait rendintipai adhyayanalu jarigaayi.
down syndrome.
gartphace down syndromtho mudipadi undani anumaanistunnaaru. trifunctional protein human gars-airs-gaartnu encoding chese janyuvu down syndrome klishtamaina praantamloo chromosome 21q22.1 loe undhi. down syndrome unna vyaktula prasavaanantara abhivruddhi samayamlo protein cerebellumlo atigaa vyakteekarinchabadutundi. saadhaaranamgaa, eee protein puttina ventane cerebellumlo gurtinchabadadu, conny prenatal developmentlo adhika sthaayilo kanipistundi.

