次黄嘌呤-鸟嘌呤磷酸核苷转移酶 - Wikiwand
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次黄嘌呤-鸟嘌呤磷酸核苷转移酶

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hypoxanthine phosphoribosyltransferase
识别号
别名;HPRT
外部IDGeneCards[1]
直系同源
物种人类小鼠
Entrez
Ensembl
UniProt
mRNA​序列

n/a

n/a

蛋白序列

n/a

n/a

基因位置​(UCSC)n/an/a
PubMed​查找n/an/a
维基数据
检视/编辑 人类

次黄嘌呤-鸟嘌呤磷酸核苷转移酶(Hypoxanthine-guanine phosphoribosyltransferase,简称HGPRT)为人体内一个翻译自HPRT1基因酵素[1][2]

HGPRT为一种转移酶,可以催化将次黄嘌呤转换为肌苷酸(IMP),也可将鸟嘌呤的反应转为单磷酸鸟苷。这两个反应都是将PRPP的5-磷酸核苷转移至嘌呤上。HGPRT在核苷酸补救合成途径中扮演重要角色。

功能

hypoxanthine phosphoribosyltransferase
识别码
EC编号 2.4.2.8
CAS号
数据库
IntEnz IntEnz浏览
BRENDA英语BRENDA BRENDA入口
ExPASy英语ExPASy NiceZyme浏览
KEGG KEGG入口
MetaCyc英语MetaCyc 代谢路径
PRIAM英语PRIAM_enzyme-specific_profiles 概述
PDB RCSB PDB PDBj PDBe PDBsum
基因本体 AmiGO / EGO

HGPRT催化下列反应:

反应物 产物 备注
次黄嘌呤 肌苷酸
鸟嘌呤 单磷酸鸟苷 常称HGPRT,仅有部分物种有此功能。
黄嘌呤 单磷酸黄核苷英语xanthosine monophosphate 特定HPRT

HGPRTase functions primarily to salvage purines from degraded DNA to reintroduce into purine synthetic pathways. In this role, it catalyzes the reaction between guanine and phosphoribosyl pyrophosphate (PRPP) to form GMP, or between hypoxanthine and phosphoribosyl pyrophosphate (PRPP) to form inosine monophosphate.

Substrates and inhibitors

Comparative homology modelling of this enzyme in L. donovani英语L. donovani suggest that among all of the computationally screened compounds, pentamidine英语pentamidine, 1,3-dinitroadamantane, acyclovir and analogs of acyclovir had higher binding affinities than the real substrate (guanosine monophosphate).[3]

疾病中的角色

此基因的突变往往导致高尿酸血症

  • 一些男性带有部分程度的HGPRT缺陷(约低于正常活动量20%)并因此导致血液中高浓度的尿酸。随之而来的是痛风以及肾结石。这症状称为凯利-塞米勒综合征[4]
  • 莱希-尼亨综合征起源由HPRT1突变导致的HGPRT缺陷。[5]
  • 某些基因突变可能导致痛风。发病的风险与hypoxanthine-guanine phosphoribosyltransferase的缺陷程度成正比。
透过基因工程让一只老鼠带有缺陷的HPRT基因后,老鼠的表现。
透过基因工程让一只老鼠带有缺陷的HPRT基因后,老鼠的表现。
  • HPRT expression on the mRNA and protein level is induced by hypoxia inducible factor 1 (HIF1A英语HIF1A). HIF-1 is a transcription factor that directs an array of cellular responses that are used for adaptation during oxygen deprivation. This finding implies that HPRT is a critical pathway that helps preserve the cell's purine nucleotide resources under hypoxic conditions as found in pathology such as myocardial ischemia.[6]

The in silico and in-vitro correlation of these compounds were test in Leishmania HGPRT and validates the result.[7]

Hybridomas

Hybridoma英语Hybridomas are immortal (immune to cellular senescence英语cellular senescence), HGPRT+ cells that result from fusion of mortal, HGPRT+ plasma cells and immortal, HGPRT myeloma cells. They are created to produce monoclonal antibodies in biotechnology. HAT medium英语HAT medium inhibits de novo synthesis of nucleic acids, killing myeloma cells that cannot switch over to the salvage pathway, due to lack of HRPT1. The plasma cells in the culture eventually die from senesence, leaving pure hybridoma cells.

参见

参考文献

  1. ^ Entrez Gene: hypoxanthine phosphoribosyltransferase 1 (Lesch-Nyhan syndrome). 
  2. ^ Finette BA, Kendall H, Vacek PM. Mutational spectral analysis at the HPRT locus in healthy children. Mutation Research. Aug 2002, 505 (1-2): 27–41. PMID 12175903. doi:10.1016/S0027-5107(02)00119-7. 
  3. ^ Ansari MY, Dikhit MR, Sahoo GC, Das P. Comparative modeling of HGPRT enzyme of L. donovani and binding affinities of different analogs of GMP. International Journal of Biological Macromolecules. Apr 2012, 50 (3): 637–49. PMID 22327112. doi:10.1016/j.ijbiomac.2012.01.010. 
  4. ^ Khattak FH, Morris IM, Harris K. Kelley-Seegmiller syndrome: a case report and review of the literature. British Journal of Rheumatology. May 1998, 37 (5): 580–1. PMID 9651092. doi:10.1093/rheumatology/37.5.580c. 
  5. ^ Hladnik U, Nyhan WL, Bertelli M. Variable expression of HPRT deficiency in 5 members of a family with the same mutation. Archives of Neurology. Sep 2008, 65 (9): 1240–3. PMID 18779430. doi:10.1001/archneur.65.9.1240. 
  6. ^ Wu J, Bond C, Chen P, Chen M, Li Y, Shohet RV, Wright G. HIF-1α in the heart: Remodeling nucleotide metabolism. Journal of Molecular and Cellular Cardiology. Feb 2015, 82: 194–200. PMID 25681585. doi:10.1016/j.yjmcc.2015.01.014. 
  7. ^ Ansari MY, Equbal A, Dikhit MR, Mansuri R, Rana S, Ali V, Sahoo GC, Das P. Establishment of Correlation between In-Silico &In-Vitro Test Analysis against Leishmania HGPRT to inhibitors. International Journal of Biological Macromolecules. Nov 2015, 83: 78–96. PMID 26616453. doi:10.1016/j.ijbiomac.2015.11.051. 

延伸阅读

外部链接

Category:EC 2.4.2英语Category:EC 2.4.2

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次黄嘌呤-鸟嘌呤磷酸核苷转移酶
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