2vd4
From Proteopedia
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| - | [[Image:2vd4.jpg|left|200px]] | + | [[Image:2vd4.jpg|left|200px]] |
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| - | '''STRUCTURE OF SMALL-MOLECULE INHIBITOR OF GLMU FROM HAEMOPHILUS INFLUENZAE REVEALS AN ALLOSTERIC BINDING SITE''' | + | {{Structure |
| + | |PDB= 2vd4 |SIZE=350|CAPTION= <scene name='initialview01'>2vd4</scene>, resolution 1.90Å | ||
| + | |SITE= <scene name='pdbsite=AC1:P21+Binding+Site+For+Chain+A'>AC1</scene>, <scene name='pdbsite=AC2:So4+Binding+Site+For+Chain+A'>AC2</scene>, <scene name='pdbsite=AC3:So4+Binding+Site+For+Chain+A'>AC3</scene>, <scene name='pdbsite=AC4:So4+Binding+Site+For+Chain+A'>AC4</scene>, <scene name='pdbsite=AC5:So4+Binding+Site+For+Chain+A'>AC5</scene>, <scene name='pdbsite=AC6:So4+Binding+Site+For+Chain+A'>AC6</scene>, <scene name='pdbsite=AC7:So4+Binding+Site+For+Chain+A'>AC7</scene>, <scene name='pdbsite=AC8:Pg4+Binding+Site+For+Chain+A'>AC8</scene>, <scene name='pdbsite=AC9:Pg4+Binding+Site+For+Chain+A'>AC9</scene>, <scene name='pdbsite=BC1:Pge+Binding+Site+For+Chain+A'>BC1</scene>, <scene name='pdbsite=BC2:Mg+Binding+Site+For+Chain+A'>BC2</scene> and <scene name='pdbsite=BC3:Mg+Binding+Site+For+Chain+A'>BC3</scene> | ||
| + | |LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=P21:4-chloro-N-(3-methoxypropyl)-N-[(3S)-1-(2-phenylethyl)piperidin-3-yl]benzamide'>P21</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene> and <scene name='pdbligand=PGE:TRIETHYLENE GLYCOL'>PGE</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''STRUCTURE OF SMALL-MOLECULE INHIBITOR OF GLMU FROM HAEMOPHILUS INFLUENZAE REVEALS AN ALLOSTERIC BINDING SITE''' | ||
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==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2VD4 is a [ | + | 2VD4 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Haemophilus_influenzae Haemophilus influenzae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VD4 OCA]. |
==Reference== | ==Reference== | ||
| - | Structure of a small-molecule inhibitor complexed with GlmU from Haemophilus influenzae reveals an allosteric binding site., Mochalkin I, Lightle S, Narasimhan L, Bornemeier D, Melnick M, Vanderroest S, McDowell L, Protein Sci. 2008 Mar;17(3):577-82. Epub 2008 Jan 24. PMID:[http:// | + | Structure of a small-molecule inhibitor complexed with GlmU from Haemophilus influenzae reveals an allosteric binding site., Mochalkin I, Lightle S, Narasimhan L, Bornemeier D, Melnick M, Vanderroest S, McDowell L, Protein Sci. 2008 Mar;17(3):577-82. Epub 2008 Jan 24. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18218712 18218712] |
[[Category: Haemophilus influenzae]] | [[Category: Haemophilus influenzae]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: uridyltransferase]] | [[Category: uridyltransferase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:45:33 2008'' |
Revision as of 16:45, 20 March 2008
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| , resolution 1.90Å | |||||||
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| Sites: | , , , , , , , , , , and | ||||||
| Ligands: | , , , and | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
STRUCTURE OF SMALL-MOLECULE INHIBITOR OF GLMU FROM HAEMOPHILUS INFLUENZAE REVEALS AN ALLOSTERIC BINDING SITE
Overview
N-Acetylglucosamine-1-phosphate uridyltransferase (GlmU) is an essential enzyme in aminosugars metabolism and an attractive target for antibiotic drug discovery. GlmU catalyzes the formation of uridine-diphospho-N-acetylglucosamine (UDP-GlcNAc), an important precursor in the peptidoglycan and lipopolisaccharide biosynthesis in both Gram-negative and Gram-positive bacteria. Here we disclose a 1.9 A resolution crystal structure of a synthetic small-molecule inhibitor of GlmU from Haemophilus influenzae (hiGlmU). The compound was identified through a high-throughput screening (HTS) configured to detect inhibitors that target the uridyltransferase active site of hiGlmU. The original HTS hit exhibited a modest micromolar potency (IC(50) approximately 18 muM in a racemic mixture) against hiGlmU and no activity against Staphylococcus aureus GlmU (saGlmU). The determined crystal structure indicated that the inhibitor occupies an allosteric site adjacent to the GlcNAc-1-P substrate-binding region. Analysis of the mechanistic model of the uridyltransferase reaction suggests that the binding of this allosteric inhibitor prevents structural rearrangements that are required for the enzymatic reaction, thus providing a basis for structure-guided design of a new class of mechanism-based inhibitors of GlmU.
About this Structure
2VD4 is a Single protein structure of sequence from Haemophilus influenzae. Full crystallographic information is available from OCA.
Reference
Structure of a small-molecule inhibitor complexed with GlmU from Haemophilus influenzae reveals an allosteric binding site., Mochalkin I, Lightle S, Narasimhan L, Bornemeier D, Melnick M, Vanderroest S, McDowell L, Protein Sci. 2008 Mar;17(3):577-82. Epub 2008 Jan 24. PMID:18218712
Page seeded by OCA on Thu Mar 20 18:45:33 2008
Categories: Haemophilus influenzae | Single protein | Lightle, S. | Mcdowell, L. | Mochalkin, I. | MG | P21 | PG4 | PGE | SO4 | Active site | Acyltransferase | Allosteric | Cell shape | Cell wall biogenesis/degradation | Cytoplasm | Glmu | Inhibitor | Magnesium | Metal-binding | Multifunctional enzyme | Nucleotidyltransferase | Peptidoglycan synthesis | Transferase | Uridyltransferase
