2vd4

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[[Image:2vd4.jpg|left|200px]]
[[Image:2vd4.jpg|left|200px]]
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{{Structure
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<!--
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|PDB= 2vd4 |SIZE=350|CAPTION= <scene name='initialview01'>2vd4</scene>, resolution 1.90&Aring;
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The line below this paragraph, containing "STRUCTURE_2vd4", creates the "Structure Box" on the page.
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|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>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <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>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY=
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or leave the SCENE parameter empty for the default display.
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|GENE=
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-->
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|DOMAIN=
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{{STRUCTURE_2vd4| PDB=2vd4 | SCENE= }}
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|RELATEDENTRY=[[2v0i|2V0I]], [[2v0l|2V0L]], [[2v0h|2V0H]], [[2v0j|2V0J]], [[2v0k|2V0K]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2vd4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vd4 OCA], [http://www.ebi.ac.uk/pdbsum/2vd4 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2vd4 RCSB]</span>
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}}
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'''STRUCTURE OF SMALL-MOLECULE INHIBITOR OF GLMU FROM HAEMOPHILUS INFLUENZAE REVEALS AN ALLOSTERIC BINDING SITE'''
'''STRUCTURE OF SMALL-MOLECULE INHIBITOR OF GLMU FROM HAEMOPHILUS INFLUENZAE REVEALS AN ALLOSTERIC BINDING SITE'''
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[[Category: Mcdowell, L.]]
[[Category: Mcdowell, L.]]
[[Category: Mochalkin, I.]]
[[Category: Mochalkin, I.]]
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[[Category: active site]]
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[[Category: Active site]]
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[[Category: acyltransferase]]
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[[Category: Acyltransferase]]
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[[Category: allosteric]]
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[[Category: Allosteric]]
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[[Category: cell shape]]
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[[Category: Cell shape]]
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[[Category: cell wall biogenesis/degradation]]
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[[Category: Cell wall biogenesis/degradation]]
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[[Category: cytoplasm]]
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[[Category: Cytoplasm]]
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[[Category: glmu]]
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[[Category: Glmu]]
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[[Category: inhibitor]]
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[[Category: Inhibitor]]
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[[Category: magnesium]]
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[[Category: Magnesium]]
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[[Category: metal-binding]]
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[[Category: Metal-binding]]
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[[Category: multifunctional enzyme]]
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[[Category: Multifunctional enzyme]]
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[[Category: nucleotidyltransferase]]
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[[Category: Nucleotidyltransferase]]
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[[Category: peptidoglycan synthesis]]
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[[Category: Peptidoglycan synthesis]]
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[[Category: transferase]]
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[[Category: Transferase]]
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[[Category: uridyltransferase]]
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[[Category: Uridyltransferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 18:37:13 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:11:01 2008''
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Revision as of 15:37, 4 May 2008

Image:2vd4.jpg

Template:STRUCTURE 2vd4

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 Sun May 4 18:37:13 2008

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OCA

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