1cjb

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[[Image:1cjb.gif|left|200px]]<br /><applet load="1cjb" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1cjb.gif|left|200px]]
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caption="1cjb, resolution 2.00&Aring;" />
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'''MALARIAL PURINE PHOSPHORIBOSYLTRANSFERASE'''<br />
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{{Structure
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|PDB= 1cjb |SIZE=350|CAPTION= <scene name='initialview01'>1cjb</scene>, resolution 2.00&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=IRP:(1S)-1(9-DEAZAHYPOXANTHIN-9YL)1,4-DIDEOXY-1,4-IMINO-D-RIBITOL-5-PHOSPHATE'>IRP</scene> and <scene name='pdbligand=POP:PYROPHOSPHATE 2-'>POP</scene>
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|ACTIVITY= [http://en.wikipedia.org/wiki/Hypoxanthine_phosphoribosyltransferase Hypoxanthine phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.8 2.4.2.8]
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|GENE=
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}}
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'''MALARIAL PURINE PHOSPHORIBOSYLTRANSFERASE'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1CJB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=IRP:'>IRP</scene> and <scene name='pdbligand=POP:'>POP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Hypoxanthine_phosphoribosyltransferase Hypoxanthine phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.8 2.4.2.8] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CJB OCA].
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1CJB is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CJB OCA].
==Reference==
==Reference==
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The 2.0 A structure of malarial purine phosphoribosyltransferase in complex with a transition-state analogue inhibitor., Shi W, Li CM, Tyler PC, Furneaux RH, Cahill SM, Girvin ME, Grubmeyer C, Schramm VL, Almo SC, Biochemistry. 1999 Aug 3;38(31):9872-80. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10433693 10433693]
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The 2.0 A structure of malarial purine phosphoribosyltransferase in complex with a transition-state analogue inhibitor., Shi W, Li CM, Tyler PC, Furneaux RH, Cahill SM, Girvin ME, Grubmeyer C, Schramm VL, Almo SC, Biochemistry. 1999 Aug 3;38(31):9872-80. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10433693 10433693]
[[Category: Hypoxanthine phosphoribosyltransferase]]
[[Category: Hypoxanthine phosphoribosyltransferase]]
[[Category: Plasmodium falciparum]]
[[Category: Plasmodium falciparum]]
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[[Category: transition state inhibitor]]
[[Category: transition state inhibitor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:06:39 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:25:08 2008''

Revision as of 08:25, 20 March 2008

Image:1cjb.gif


PDB ID 1cjb

Drag the structure with the mouse to rotate
, resolution 2.00Å
Ligands: , and
Activity: Hypoxanthine phosphoribosyltransferase, with EC number 2.4.2.8
Coordinates: save as pdb, mmCIF, xml



MALARIAL PURINE PHOSPHORIBOSYLTRANSFERASE


Overview

Malaria is a leading cause of worldwide mortality from infectious disease. Plasmodium falciparum proliferation in human erythrocytes requires purine salvage by hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRTase). The enzyme is a target for the development of novel antimalarials. Design and synthesis of transition-state analogue inhibitors permitted cocrystallization with the malarial enzyme and refinement of the complex to 2.0 A resolution. Catalytic site contacts in the malarial enzyme are similar to those of human hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) despite distinct substrate specificity. The crystal structure of malarial HGXPRTase with bound inhibitor, pyrophosphate, and two Mg(2+) ions reveals features unique to the transition-state analogue complex. Substrate-assisted catalysis occurs by ribooxocarbenium stabilization from the O5' lone pair and a pyrophosphate oxygen. A dissociative reaction coordinate path is implicated in which the primary reaction coordinate motion is the ribosyl C1' in motion between relatively immobile purine base and (Mg)(2)-pyrophosphate. Several short hydrogen bonds form in the complex of the enzyme and inhibitor. The proton NMR spectrum of the transition-state analogue complex of malarial HGXPRTase contains two downfield signals at 14.3 and 15.3 ppm. Despite the structural similarity to the human enzyme, the NMR spectra of the complexes reveal differences in hydrogen bonding between the transition-state analogue complexes of the human and malarial HG(X)PRTases. The X-ray crystal structures and NMR spectra reveal chemical and structural features that suggest a strategy for the design of malaria-specific transition-state inhibitors.

About this Structure

1CJB is a Single protein structure of sequence from Plasmodium falciparum. Full crystallographic information is available from OCA.

Reference

The 2.0 A structure of malarial purine phosphoribosyltransferase in complex with a transition-state analogue inhibitor., Shi W, Li CM, Tyler PC, Furneaux RH, Cahill SM, Girvin ME, Grubmeyer C, Schramm VL, Almo SC, Biochemistry. 1999 Aug 3;38(31):9872-80. PMID:10433693

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