1n3i
From Proteopedia
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|PDB= 1n3i |SIZE=350|CAPTION= <scene name='initialview01'>1n3i</scene>, resolution 1.90Å | |PDB= 1n3i |SIZE=350|CAPTION= <scene name='initialview01'>1n3i</scene>, resolution 1.90Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=DIH:3-HYDROXY-4-HYDROXYMETHYL-1-(4-OXO-4,4A,5,7A-TETRAHYDRO-3H-PYRROLO[3,2-D]PYRIMIDIN-7-YLMETHYL)-PYRROLIDINIUM'>DIH</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Purine-nucleoside_phosphorylase Purine-nucleoside phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.1 2.4.2.1] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Purine-nucleoside_phosphorylase Purine-nucleoside phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.1 2.4.2.1] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1g2o|1G2O]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1n3i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n3i OCA], [http://www.ebi.ac.uk/pdbsum/1n3i PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1n3i RCSB]</span> | ||
}} | }} | ||
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[[Category: Shi, W.]] | [[Category: Shi, W.]] | ||
[[Category: Tyler, P C.]] | [[Category: Tyler, P C.]] | ||
| - | [[Category: DIH]] | ||
| - | [[Category: PO4]] | ||
[[Category: pnp]] | [[Category: pnp]] | ||
[[Category: transition state complex]] | [[Category: transition state complex]] | ||
[[Category: trimer]] | [[Category: trimer]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:24:50 2008'' |
Revision as of 19:24, 30 March 2008
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| , resolution 1.90Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Activity: | Purine-nucleoside phosphorylase, with EC number 2.4.2.1 | ||||||
| Related: | 1G2O
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of Mycobacterium tuberculosis PNP with transition state analog DADMe-ImmH
Overview
Stable chemical analogues of enzymatic transition states are imperfect mimics since they lack the partial bond character of the transition state. We synthesized structural variants of the Immucillins as transition state analogues for purine nucleoside phosphorylase and characterized them with the enzyme from Mycobacterium tuberculosis (MtPNP). PNPs form transition states with ribooxacarbenium ion character and catalyze nucleophilic displacement reactions by migration of the cationic ribooxacarbenium carbon between the enzymatically immobilized purine and phosphate nucleophiles. As bond-breaking progresses, carbocation character builds on the ribosyl group, the distance between the purine and the carbocation increases, and the distance between carbocation and phosphate anion decreases. Transition state analogues were produced with carbocation character and increased distance between the ribooxacarbenium ion and the purine mimics by incorporating a methylene bridge between these groups. Immucillin-H (ImmH), DADMe-ImmH, and DADMe-ImmG mimic the transition state of MtPNP and are slow-onset, tight-binding inhibitors of MtPNP with equilibrium dissociation constants of 650, 42, and 24 pM. Crystal structures of MtPNP complexes with ImmH and DADMe-ImmH reveal an ion-pair between the inhibitor cation and the nucleophilic phosphoryl anion. The stronger ion-pair (2.7 A) is found with DADMe-ImmH. The position of bound ImmH resembles the substrate side of the transition state barrier, and DADMe-ImmH more closely resembles the product side of the barrier. The ability to probe both substrate and product sides of the transition state barrier provides expanded opportunities to explore transition state analogue design in N-ribosyltransferases. This approach has resulted in the highest affinity transition state analogues known for MtPNP.
About this Structure
1N3I is a Single protein structure of sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA.
Reference
Over-the-barrier transition state analogues and crystal structure with Mycobacterium tuberculosis purine nucleoside phosphorylase., Lewandowicz A, Shi W, Evans GB, Tyler PC, Furneaux RH, Basso LA, Santos DS, Almo SC, Schramm VL, Biochemistry. 2003 May 27;42(20):6057-66. PMID:12755607
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