1g95
From Proteopedia
(New page: 200px<br /><applet load="1g95" size="450" color="white" frame="true" align="right" spinBox="true" caption="1g95, resolution 2.33Å" /> '''CRYSTAL STRUCTURE OF...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1g95.jpg|left|200px]]<br /><applet load="1g95" size=" | + | [[Image:1g95.jpg|left|200px]]<br /><applet load="1g95" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1g95, resolution 2.33Å" /> | caption="1g95, resolution 2.33Å" /> | ||
'''CRYSTAL STRUCTURE OF S.PNEUMONIAE GLMU, APO FORM'''<br /> | '''CRYSTAL STRUCTURE OF S.PNEUMONIAE GLMU, APO FORM'''<br /> | ||
==Overview== | ==Overview== | ||
| - | N-Acetylglucosamine-1-phosphate uridyltransferase (GlmU) is an essential | + | N-Acetylglucosamine-1-phosphate uridyltransferase (GlmU) is an essential bacterial enzyme with both an acetyltransferase and a uridyltransferase activity which have been mapped to the C-terminal and N-terminal domains, respectively. GlmU performs the last two steps in the synthesis of UDP-N-acetylglucosamine (UDP-GlcNAc), which is an essential precursor in both the peptidoglycan and the lipopolysaccharide metabolic pathways. GlmU is therefore an attractive target for potential antibiotics. Knowledge of its three-dimensional structure would provide a basis for rational drug design. We have determined the crystal structures of Streptococcus pneumoniae GlmU (SpGlmU) in apo form at 2.33 A resolution, and in complex with UDP-N-acetyl glucosamine and the essential co-factor Mg(2+) at 1.96 A resolution. The protein structure consists of an N-terminal domain with an alpha/beta-fold, containing the uridyltransferase active site, and a C-terminal domain with a long left-handed beta-sheet helix (LbetaH) domain. An insertion loop containing the highly conserved sequence motif Asn-Tyr-Asp-Gly protrudes from the left-handed beta-sheet helix domain. In the crystal, S. pneumoniae GlmU forms exact trimers, mainly through contacts between left-handed beta-sheet helix domains. UDP-N-acetylglucosamine and Mg(2+) are bound at the uridyltransferase active site, which is in a closed form. We propose a uridyltransferase mechanism in which the activation energy of the double negatively charged phosphorane transition state is lowered by charge compensation of Mg(2+) and the side-chain of Lys22. |
==About this Structure== | ==About this Structure== | ||
| - | 1G95 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptococcus_pneumoniae Streptococcus pneumoniae]. Active as [http://en.wikipedia.org/wiki/UDP-N-acetylglucosamine_diphosphorylase UDP-N-acetylglucosamine diphosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.23 2.7.7.23] Full crystallographic information is available from [http:// | + | 1G95 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptococcus_pneumoniae Streptococcus pneumoniae]. Active as [http://en.wikipedia.org/wiki/UDP-N-acetylglucosamine_diphosphorylase UDP-N-acetylglucosamine diphosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.23 2.7.7.23] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G95 OCA]. |
==Reference== | ==Reference== | ||
| Line 14: | Line 14: | ||
[[Category: Streptococcus pneumoniae]] | [[Category: Streptococcus pneumoniae]] | ||
[[Category: UDP-N-acetylglucosamine diphosphorylase]] | [[Category: UDP-N-acetylglucosamine diphosphorylase]] | ||
| - | [[Category: Arcy, A | + | [[Category: Arcy, A D.]] |
[[Category: Kamber, M.]] | [[Category: Kamber, M.]] | ||
[[Category: Kostrewa, D.]] | [[Category: Kostrewa, D.]] | ||
| Line 23: | Line 23: | ||
[[Category: uridyltransferase pyrophosphorylase]] | [[Category: uridyltransferase pyrophosphorylase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:47:29 2008'' |
Revision as of 10:47, 21 February 2008
|
CRYSTAL STRUCTURE OF S.PNEUMONIAE GLMU, APO FORM
Overview
N-Acetylglucosamine-1-phosphate uridyltransferase (GlmU) is an essential bacterial enzyme with both an acetyltransferase and a uridyltransferase activity which have been mapped to the C-terminal and N-terminal domains, respectively. GlmU performs the last two steps in the synthesis of UDP-N-acetylglucosamine (UDP-GlcNAc), which is an essential precursor in both the peptidoglycan and the lipopolysaccharide metabolic pathways. GlmU is therefore an attractive target for potential antibiotics. Knowledge of its three-dimensional structure would provide a basis for rational drug design. We have determined the crystal structures of Streptococcus pneumoniae GlmU (SpGlmU) in apo form at 2.33 A resolution, and in complex with UDP-N-acetyl glucosamine and the essential co-factor Mg(2+) at 1.96 A resolution. The protein structure consists of an N-terminal domain with an alpha/beta-fold, containing the uridyltransferase active site, and a C-terminal domain with a long left-handed beta-sheet helix (LbetaH) domain. An insertion loop containing the highly conserved sequence motif Asn-Tyr-Asp-Gly protrudes from the left-handed beta-sheet helix domain. In the crystal, S. pneumoniae GlmU forms exact trimers, mainly through contacts between left-handed beta-sheet helix domains. UDP-N-acetylglucosamine and Mg(2+) are bound at the uridyltransferase active site, which is in a closed form. We propose a uridyltransferase mechanism in which the activation energy of the double negatively charged phosphorane transition state is lowered by charge compensation of Mg(2+) and the side-chain of Lys22.
About this Structure
1G95 is a Single protein structure of sequence from Streptococcus pneumoniae. Active as UDP-N-acetylglucosamine diphosphorylase, with EC number 2.7.7.23 Full crystallographic information is available from OCA.
Reference
Crystal structures of Streptococcus pneumoniae N-acetylglucosamine-1-phosphate uridyltransferase, GlmU, in apo form at 2.33 A resolution and in complex with UDP-N-acetylglucosamine and Mg(2+) at 1.96 A resolution., Kostrewa D, D'Arcy A, Takacs B, Kamber M, J Mol Biol. 2001 Jan 12;305(2):279-89. PMID:11124906
Page seeded by OCA on Thu Feb 21 12:47:29 2008
