2q3c: Difference between revisions
New page: left|200px<br /><applet load="2q3c" size="450" color="white" frame="true" align="right" spinBox="true" caption="2q3c, resolution 2.10Å" /> '''2.1 A Resolution Cry... |
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[[Image:2q3c.gif|left|200px]]<br /><applet load="2q3c" size=" | [[Image:2q3c.gif|left|200px]]<br /><applet load="2q3c" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="2q3c, resolution 2.10Å" /> | caption="2q3c, resolution 2.10Å" /> | ||
'''2.1 A Resolution Crystal Structure of O-Acetylserine Sulfhydrylase (OASS) Holoenzyme From MYCOBACTERIUM TUBERCULOSIS in Complex with the Inhibitory Peptide DFSI'''<br /> | '''2.1 A Resolution Crystal Structure of O-Acetylserine Sulfhydrylase (OASS) Holoenzyme From MYCOBACTERIUM TUBERCULOSIS in Complex with the Inhibitory Peptide DFSI'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
2Q3C is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with MPD as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Cysteine_synthase Cysteine synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.47 2.5.1.47] Full crystallographic information is available from [http:// | 2Q3C is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with <scene name='pdbligand=MPD:'>MPD</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Cysteine_synthase Cysteine synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.47 2.5.1.47] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q3C OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: sulphur metabolism]] | [[Category: sulphur metabolism]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 13:57:32 2008'' | ||
Revision as of 14:57, 23 January 2008
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2.1 A Resolution Crystal Structure of O-Acetylserine Sulfhydrylase (OASS) Holoenzyme From MYCOBACTERIUM TUBERCULOSIS in Complex with the Inhibitory Peptide DFSI
OverviewOverview
Cysteine biosynthetic genes are up-regulated in the persistent phase of, Mycobacterium tuberculosis, and the corresponding enzymes are therefore of, interest as potential targets for novel antibacterial agents. cysK1 is one, of these genes and has been annotated as coding for an O-acetylserine, sulfhydrylase. Recombinant CysK1 is a pyridoxal phosphate (PLP)-dependent, enzyme that catalyzes the conversion of O-acetylserine to cysteine. The, crystal structure of the enzyme was determined to 1.8A resolution. CysK1, belongs to the family of fold type II PLP enzymes and is similar in, structure to other O-acetylserine sulfhydrylases. We were able to trap the, alpha-aminoacrylate reaction intermediate and determine its structure by, cryocrystallography. Formation of the aminoacrylate complex is accompanied, by a domain rotation resulting in active site closure. The aminoacrylate, moiety is bound in the active site via the covalent linkage to the PLP, cofactor and by hydrogen bonds of its carboxyl group to several enzyme, residues. The catalytic lysine residue is positioned such that it can, protonate the Calpha-carbon atom of the aminoacrylate only from the, si-face, resulting in the formation of l-cysteine. CysK1 is competitively, inhibited by a four-residue peptide derived from the C-terminal of serine, acetyl transferase. The crystallographic analysis reveals that the peptide, binds to the enzyme active site, suggesting that CysK1 forms an bi-enzyme, complex with serine acetyl transferase, in a similar manner to other, bacterial and plant O-acetylserine sulfhydrylases. The structure of the, enzyme-peptide complex provides a framework for the design of strong, binding inhibitors.
About this StructureAbout this Structure
2Q3C is a Single protein structure of sequence from Mycobacterium tuberculosis with as ligand. Active as Cysteine synthase, with EC number 2.5.1.47 Full crystallographic information is available from OCA.
ReferenceReference
Structural Insights into Catalysis and Inhibition of O-Acetylserine Sulfhydrylase from Mycobacterium tuberculosis: CRYSTAL STRUCTURES OF THE ENZYME {alpha}-AMINOACRYLATE INTERMEDIATE AND AN ENZYME-INHIBITOR COMPLEX., Schnell R, Oehlmann W, Singh M, Schneider G, J Biol Chem. 2007 Aug 10;282(32):23473-81. Epub 2007 Jun 13. PMID:17567578
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