Bifunctional purine biosynthesis protein PURH

Function

Bifunctional purine biosynthesis protein PURH (PURH) is a bifunctional enzyme which catalyzes the last two steps in purine biosynthesis. PURH is composed of 2 functionally independent domains linked by a flexible domain. The N-terminal domain possesses IMP cyclohydrolase activity (see also Cyclohydrolase) and the C-terminal domain possesses aminoimidazole 4-carboxamide ribonucleotide transformylase activity^[1].

Aminoimidazole 4-carboxamide-4-carboxylic acid (AICAR) is an allosteric activator of AMP-activated protein kinase.

Relevance

Purine biosynthesis anti-folate inhibitors, amongst them PURH inhibitors, are widely used as anti-cancer therapy^[2].

Structural highlights

The 3D structure of human PURH shows the and the ^[3]. Water molecules are shown as red spheres.

Human PURH dimer complex with activator AICAR, XMP, inhibitor and K+ ion (purple) (PDB code 1p4r)

Drag the structure with the mouse to rotate

3D structures of bifunctional purine biosynthesis protein PURH3D structures of bifunctional purine biosynthesis protein PURH

Updated on 30-May-2024

1pkx - hPURH + XMP - human
5uy8, 5uz0 - hPURH + AICAR + inhibitor
1p4r, 1pl0 - hPURH + AICAR + XMP + inhibitor
1oz0 - cPURH - chicken
1thz, 2iu3, 2iu0, 2b1g, 2b1i - cPURH + inhibitor
1m9n - cPURH + AICAR + XMP
1zcz - PURH - Thermotoga maritima
3zzm - MtPURH + CFAIR - Mycobacterium tuberculosis
4a1o - MtPURH + AICAR + CFAIR
2ntm - MetPURH - Methanothermobacter thermautotrophicus
2ntl - MetPURH + AICAR
2ntk - MetPURH + IMP

ReferencesReferences

↑ Qiu X, Yuan Y, Gao Y. Expression, purification, crystallization and preliminary X-ray diffraction crystallographic study of PurH from Escherichia coli. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011 Dec 1;67(Pt 12):1590-4., doi: 10.1107/S1744309111039960. Epub 2011 Nov 26. PMID:22139174 doi:http://dx.doi.org/10.1107/S1744309111039960
↑ McGuire JJ. Anticancer antifolates: current status and future directions. Curr Pharm Des. 2003;9(31):2593-613. doi: 10.2174/1381612033453712. PMID:14529544 doi:http://dx.doi.org/10.2174/1381612033453712
↑ Cheong CG, Wolan DW, Greasley SE, Horton PA, Beardsley GP, Wilson IA. Crystal structures of human bifunctional enzyme aminoimidazole-4-carboxamide ribonucleotide transformylase/IMP cyclohydrolase in complex with potent sulfonyl-containing antifolates. J Biol Chem. 2004 Apr 23;279(17):18034-45. Epub 2004 Feb 13. PMID:14966129 doi:10.1074/jbc.M313691200

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Michal Harel, Alexander Berchansky

[1] Qiu X, Yuan Y, Gao Y. Expression, purification, crystallization and preliminary X-ray diffraction crystallographic study of PurH from Escherichia coli. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011 Dec 1;67(Pt 12):1590-4., doi: 10.1107/S1744309111039960. Epub 2011 Nov 26. PMID:22139174 doi:http://dx.doi.org/10.1107/S1744309111039960

[2] McGuire JJ. Anticancer antifolates: current status and future directions. Curr Pharm Des. 2003;9(31):2593-613. doi: 10.2174/1381612033453712. PMID:14529544 doi:http://dx.doi.org/10.2174/1381612033453712

[3] Cheong CG, Wolan DW, Greasley SE, Horton PA, Beardsley GP, Wilson IA. Crystal structures of human bifunctional enzyme aminoimidazole-4-carboxamide ribonucleotide transformylase/IMP cyclohydrolase in complex with potent sulfonyl-containing antifolates. J Biol Chem. 2004 Apr 23;279(17):18034-45. Epub 2004 Feb 13. PMID:14966129 doi:10.1074/jbc.M313691200

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