1l4u
From Proteopedia
(New page: 200px<br /><applet load="1l4u" size="450" color="white" frame="true" align="right" spinBox="true" caption="1l4u, resolution 1.80Å" /> '''CRYSTAL STRUCTURE OF...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1l4u.gif|left|200px]]<br /><applet load="1l4u" size=" | + | [[Image:1l4u.gif|left|200px]]<br /><applet load="1l4u" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1l4u, resolution 1.80Å" /> | caption="1l4u, resolution 1.80Å" /> | ||
'''CRYSTAL STRUCTURE OF SHIKIMATE KINASE FROM MYCOBACTERIUM TUBERCULOSIS IN COMPLEX WITH MGADP AND PT(II) AT 1.8 ANGSTROM RESOLUTION'''<br /> | '''CRYSTAL STRUCTURE OF SHIKIMATE KINASE FROM MYCOBACTERIUM TUBERCULOSIS IN COMPLEX WITH MGADP AND PT(II) AT 1.8 ANGSTROM RESOLUTION'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Shikimate kinase (SK) and other enzymes in the shikimate pathway are | + | Shikimate kinase (SK) and other enzymes in the shikimate pathway are potential targets for developing non-toxic antimicrobial agents, herbicides, and anti-parasite drugs, because the pathway is essential in the above species but is absent from mammals. The crystal structure of Mycobacterium tuberculosis SK (MtSK) in complex with MgADP has been determined at 1.8 A resolution, revealing critical information for the structure-based design of novel anti-M. tuberculosis agents. MtSK, with a five-stranded parallel beta-sheet flanked by eight alpha-helices, has three domains: the CORE domain, the shikimate-binding domain (SB), and the LID domain. The ADP molecule is bound with its adenine moiety sandwiched between the side-chains of Arg110 and Pro155, its beta-phosphate group in the P-loop, and the alpha and beta-phosphate groups hydrogen bonded to the guanidinium group of Arg117. Arg117 is located in the LID domain, is strictly conserved in SK sequences, is observed for the first time to interact with any bound nucleotide, and appears to be important in both substrate binding and catalysis. The crystal structure of MtSK (this work) and that of Erwinia chrysanthemi SK suggest a concerted conformational change of the LID and SB domains upon nucleotide binding. |
==About this Structure== | ==About this Structure== | ||
| - | 1L4U 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 PT, MG, CL, ADP and EPE as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Shikimate_kinase Shikimate kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.71 2.7.1.71] Full crystallographic information is available from [http:// | + | 1L4U 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=PT:'>PT</scene>, <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=ADP:'>ADP</scene> and <scene name='pdbligand=EPE:'>EPE</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Shikimate_kinase Shikimate kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.71 2.7.1.71] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L4U OCA]. |
==Reference== | ==Reference== | ||
| Line 32: | Line 32: | ||
[[Category: x-ray crystallography]] | [[Category: x-ray crystallography]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:41:18 2008'' |
Revision as of 11:41, 21 February 2008
|
CRYSTAL STRUCTURE OF SHIKIMATE KINASE FROM MYCOBACTERIUM TUBERCULOSIS IN COMPLEX WITH MGADP AND PT(II) AT 1.8 ANGSTROM RESOLUTION
Overview
Shikimate kinase (SK) and other enzymes in the shikimate pathway are potential targets for developing non-toxic antimicrobial agents, herbicides, and anti-parasite drugs, because the pathway is essential in the above species but is absent from mammals. The crystal structure of Mycobacterium tuberculosis SK (MtSK) in complex with MgADP has been determined at 1.8 A resolution, revealing critical information for the structure-based design of novel anti-M. tuberculosis agents. MtSK, with a five-stranded parallel beta-sheet flanked by eight alpha-helices, has three domains: the CORE domain, the shikimate-binding domain (SB), and the LID domain. The ADP molecule is bound with its adenine moiety sandwiched between the side-chains of Arg110 and Pro155, its beta-phosphate group in the P-loop, and the alpha and beta-phosphate groups hydrogen bonded to the guanidinium group of Arg117. Arg117 is located in the LID domain, is strictly conserved in SK sequences, is observed for the first time to interact with any bound nucleotide, and appears to be important in both substrate binding and catalysis. The crystal structure of MtSK (this work) and that of Erwinia chrysanthemi SK suggest a concerted conformational change of the LID and SB domains upon nucleotide binding.
About this Structure
1L4U is a Single protein structure of sequence from Mycobacterium tuberculosis with , , , and as ligands. Active as Shikimate kinase, with EC number 2.7.1.71 Full crystallographic information is available from OCA.
Reference
Crystal structure of shikimate kinase from Mycobacterium tuberculosis reveals the dynamic role of the LID domain in catalysis., Gu Y, Reshetnikova L, Li Y, Wu Y, Yan H, Singh S, Ji X, J Mol Biol. 2002 Jun 7;319(3):779-89. PMID:12054870
Page seeded by OCA on Thu Feb 21 13:41:18 2008
Categories: Mycobacterium tuberculosis | Shikimate kinase | Single protein | Gu, Y. | Ji, X. | Li, Y. | Reshetnikova, L. | Singh, S. | Wu, Y. | Yan, H. | ADP | CL | EPE | MG | PT | Drug design | Phorsphoryl transfer | Shikimate pathway | X-ray crystallography
