1f0n
From Proteopedia
(New page: 200px<br /><applet load="1f0n" size="450" color="white" frame="true" align="right" spinBox="true" caption="1f0n, resolution 1.80Å" /> '''MYCOBACTERIUM TUBERC...) |
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| - | [[Image:1f0n.gif|left|200px]]<br /><applet load="1f0n" size=" | + | [[Image:1f0n.gif|left|200px]]<br /><applet load="1f0n" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1f0n, resolution 1.80Å" /> | caption="1f0n, resolution 1.80Å" /> | ||
'''MYCOBACTERIUM TUBERCULOSIS ANTIGEN 85B'''<br /> | '''MYCOBACTERIUM TUBERCULOSIS ANTIGEN 85B'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The Mycobacterium tuberculosis 30 kDa major secretory protein (antigen | + | The Mycobacterium tuberculosis 30 kDa major secretory protein (antigen 85B) is the most abundant protein exported by M. tuberculosis, as well as a potent immunoprotective antigen and a leading drug target. A mycolyl transferase of 285 residues, it is closely related to two other mycolyl transferases, each of molecular mass 32 kDa: antigen 85A and antigen 85C. All three catalyze transfer of the fatty acid mycolate from one trehalose monomycolate to another, resulting in trehalose dimycolate and free trehalose, thus helping to build the bacterial cell wall. We have determined two crystal structures of M. tuberculosis antigen 85B (ag85B), initially by molecular replacement using antigen 85C as a probe. The apo ag85B model is refined against 1.8 A data, to an R-factor of 0.196 (R(free) is 0.276), and includes all residues except the N-terminal Phe. The active site immobilizes a molecule of the cryoprotectant 2-methyl-2,4-pentanediol. Crystal growth with addition of trehalose resulted in a second ag85B crystal structure (1.9 A resolution; R-factor is 0.195; R(free) is 0.285). Trehalose binds in two sites at opposite ends of the active-site cleft. In our proposed mechanism model, the trehalose at the active site Ser126 represents the trehalose liberated by temporary esterification of Ser126, while the other trehalose represents the incoming trehalose monomycolate just prior to swinging over to the first trehalose site to displace the mycolate from its serine ester. Our proposed interfacial mechanism minimizes aqueous exposure of the apolar mycolates. Based on the trehalose-bound structure, we suggest a new class of antituberculous drugs, made by connecting two trehalose molecules by an amphipathic linker. |
==About this Structure== | ==About this Structure== | ||
| - | 1F0N 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 MES and MPD as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1F0N 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=MES:'>MES</scene> and <scene name='pdbligand=MPD:'>MPD</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F0N OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Anderson, D | + | [[Category: Anderson, D H.]] |
[[Category: Eisenberg, D.]] | [[Category: Eisenberg, D.]] | ||
[[Category: Harth, G.]] | [[Category: Harth, G.]] | ||
| - | [[Category: Horwitz, M | + | [[Category: Horwitz, M A.]] |
| - | [[Category: TBSGC, TB | + | [[Category: TBSGC, TB Structural Genomics Consortium.]] |
[[Category: MES]] | [[Category: MES]] | ||
[[Category: MPD]] | [[Category: MPD]] | ||
| Line 27: | Line 27: | ||
[[Category: tbsgc]] | [[Category: tbsgc]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:33:35 2008'' |
Revision as of 10:33, 21 February 2008
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MYCOBACTERIUM TUBERCULOSIS ANTIGEN 85B
Overview
The Mycobacterium tuberculosis 30 kDa major secretory protein (antigen 85B) is the most abundant protein exported by M. tuberculosis, as well as a potent immunoprotective antigen and a leading drug target. A mycolyl transferase of 285 residues, it is closely related to two other mycolyl transferases, each of molecular mass 32 kDa: antigen 85A and antigen 85C. All three catalyze transfer of the fatty acid mycolate from one trehalose monomycolate to another, resulting in trehalose dimycolate and free trehalose, thus helping to build the bacterial cell wall. We have determined two crystal structures of M. tuberculosis antigen 85B (ag85B), initially by molecular replacement using antigen 85C as a probe. The apo ag85B model is refined against 1.8 A data, to an R-factor of 0.196 (R(free) is 0.276), and includes all residues except the N-terminal Phe. The active site immobilizes a molecule of the cryoprotectant 2-methyl-2,4-pentanediol. Crystal growth with addition of trehalose resulted in a second ag85B crystal structure (1.9 A resolution; R-factor is 0.195; R(free) is 0.285). Trehalose binds in two sites at opposite ends of the active-site cleft. In our proposed mechanism model, the trehalose at the active site Ser126 represents the trehalose liberated by temporary esterification of Ser126, while the other trehalose represents the incoming trehalose monomycolate just prior to swinging over to the first trehalose site to displace the mycolate from its serine ester. Our proposed interfacial mechanism minimizes aqueous exposure of the apolar mycolates. Based on the trehalose-bound structure, we suggest a new class of antituberculous drugs, made by connecting two trehalose molecules by an amphipathic linker.
About this Structure
1F0N is a Single protein structure of sequence from Mycobacterium tuberculosis with and as ligands. Full crystallographic information is available from OCA.
Reference
An interfacial mechanism and a class of inhibitors inferred from two crystal structures of the Mycobacterium tuberculosis 30 kDa major secretory protein (Antigen 85B), a mycolyl transferase., Anderson DH, Harth G, Horwitz MA, Eisenberg D, J Mol Biol. 2001 Mar 23;307(2):671-81. PMID:11254389
Page seeded by OCA on Thu Feb 21 12:33:35 2008
Categories: Mycobacterium tuberculosis | Single protein | Anderson, D H. | Eisenberg, D. | Harth, G. | Horwitz, M A. | TBSGC, TB Structural Genomics Consortium. | MES | MPD | Mycolyl transferase; 30kda secretory protein; antigen 85b | Protein structure initiative | Psi | Structural genomics | Tb structural genomics consortium | Tbsgc
