Bifunctional purine biosynthesis protein PURH
From Proteopedia
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| - | <StructureSection load='1p4r' size='400' side='right' caption='Human PURH dimer complex with activator AICAR, XMP, inhibitor and K+ ion (purple) (PDB code [[1p4r]])' scene='84/842877/Cv/ | + | <StructureSection load='1p4r' size='400' side='right' caption='Human PURH dimer complex with activator AICAR, XMP, inhibitor and K+ ion (purple) (PDB code [[1p4r]])' scene='84/842877/Cv/2'> |
== Function == | == 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 and the C-terminal domain possesses aminoimidazole 4-carboxamide ribonucleotide transformylase activity<ref>PMID:22139174</ref>. | + | '''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<ref>PMID:22139174</ref>. |
Aminoimidazole 4-carboxamide-4-carboxylic acid (AICAR) is an allosteric activator of AMP-activated protein kinase. | Aminoimidazole 4-carboxamide-4-carboxylic acid (AICAR) is an allosteric activator of AMP-activated protein kinase. | ||
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== Structural highlights == | == Structural highlights == | ||
| - | The 3D structure of human PURH shows the XMP nucleotide bound in the IMP cyclohydrolase domain and the activator AICAR and the inhibitor bound at the interface of dimer making numerous | + | The 3D structure of human PURH shows the <scene name='84/842877/Cv/10'>XMP nucleotide bound in the IMP cyclohydrolase domain</scene> and the <scene name='84/842877/Cv/11'>activator AICAR and the inhibitor bound at the interface of dimer making numerous interactions with both PHRH monomers</scene><ref>PMID:14966129</ref>. Water molecules are shown as red spheres. |
</StructureSection> | </StructureSection> | ||
Current revision
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3D 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
References
- ↑ 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
