From Proteopedia
(Difference between revisions)
proteopedia linkproteopedia link
|
|
| Line 1: |
Line 1: |
| - | [[Image:2vef.jpg|left|200px]] | + | {{Seed}} |
| | + | [[Image:2vef.png|left|200px]] |
| | | | |
| | <!-- | | <!-- |
| Line 9: |
Line 10: |
| | {{STRUCTURE_2vef| PDB=2vef | SCENE= }} | | {{STRUCTURE_2vef| PDB=2vef | SCENE= }} |
| | | | |
| - | '''DIHYDROPTEROATE SYNTHASE FROM STREPTOCOCCUS PNEUMONIAE'''
| + | ===DIHYDROPTEROATE SYNTHASE FROM STREPTOCOCCUS PNEUMONIAE=== |
| | | | |
| | | | |
| - | ==Overview==
| + | <!-- |
| - | Dihydropteroate synthase (DHPS) catalyses an essential step in the biosynthesis of folic acid and is the target for the sulfonamide group of antimicrobial drugs. Here we report two crystal structures of DHPS from the respiratory pathogen Streptococcus pneumoniae: the apoenzyme at 1.8-A resolution and a complex with 6-hydroxymethyl-7,8-dihydropterin monophosphate at 2.4-A resolution. The enzyme forms a alpha/beta barrel structure, with a highly conserved binding pocket for recognition of the pterin substrate, 6-hydroxymethyl-7,8-dihydropterin pyrophosphate (DHPPP). There is a fixed order of substrate binding: DHPPP binds first, followed by the second substrate, para-aminobenzoic acid (pABA). Binding of pyrophosphate also allows the enzyme to recognise pABA or sulfonamide drugs, which act as pABA analogues. Using equilibrium and pre-steady state kinetic fluorescence measurements, we show that the on-rate for DHPPP binding to the enzyme is relatively slow (2.6 x 105 M-1s-1) and propose that binding of this substrate induces a large scale movement of the second loop in the enzyme structure, to participate in formation of the pABA binding site. Two mutations, which confer resistance to sulfonamide drugs, do not affect DHPPP binding but have a substantial effect on pABA and sulfonamide recognition. The results show that binding of DHPPP and pABA are separate, distinguishable events in the reaction cycle, and that mutations which confer resistance to sulfonamide drugs act exclusively on the second step in the binding process.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_18321242}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 18321242 is the PubMed ID number. |
| | + | --> |
| | + | {{ABSTRACT_PUBMED_18321242}} |
| | | | |
| | ==About this Structure== | | ==About this Structure== |
| Line 32: |
Line 36: |
| | [[Category: Streptococcus]] | | [[Category: Streptococcus]] |
| | [[Category: Transferase]] | | [[Category: Transferase]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu May 22 22:32:12 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 13:55:46 2008'' |
Revision as of 10:55, 27 July 2008
Template:STRUCTURE 2vef
DIHYDROPTEROATE SYNTHASE FROM STREPTOCOCCUS PNEUMONIAE
Template:ABSTRACT PUBMED 18321242
About this Structure
2VEF is a Single protein structure of sequence from Streptococcus pneumoniae. Full crystallographic information is available from OCA.
Reference
Dihydropteroate synthase from Streptococcus pneumoniae: structure, ligand recognition and mechanism of sulfonamide resistance., Levy C, Minnis D, Derrick JP, Biochem J. 2008 Mar 5;. PMID:18321242
Page seeded by OCA on Sun Jul 27 13:55:46 2008
