2cm1: Difference between revisions
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[[Image:2cm1. | [[Image:2cm1.jpg|left|200px]]<br /><applet load="2cm1" size="450" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="2cm1" size="450" color="white" frame="true" align="right" spinBox="true" | |||
caption="2cm1, resolution 2.00Å" /> | caption="2cm1, resolution 2.00Å" /> | ||
'''CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF SERINE THREONINE PROTEIN PHOSPHATASE PSTP IN COMPLEX WITH 2 MANGANESE IONS.'''<br /> | '''CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF SERINE THREONINE PROTEIN PHOSPHATASE PSTP IN COMPLEX WITH 2 MANGANESE IONS.'''<br /> | ||
==Overview== | |||
Phospho-Ser/Thr protein phosphatases (PPs) are dinuclear metalloenzymes, classed into two large families, PPP and PPM, on the basis of sequence, similarity and metal ion dependence. The archetype of the PPM family is, the alpha isoform of human PP2C (PP2Calpha), which folds into an, alpha/beta domain similar to those of PPP enzymes. The recent structural, studies of three bacterial PPM phosphatases, Mycobacterium tuberculosis, MtPstP, Mycobacterium smegmatis MspP, and Streptococcus agalactiae STP, confirmed the conservation of the overall fold and dinuclear metal center, in the family, but surprisingly revealed the presence of a third conserved, metal-binding site in the active site. To gain insight into the roles of, the three-metal center in bacterial enzymes, we report structural and, metal-binding studies of MtPstP and MspP. The structure of MtPstP in a new, trigonal crystal form revealed a fully active enzyme with the canonical, dinuclear metal center but without the third metal ion bound to the, catalytic site. The absence of metal correlates with a partially, unstructured flap segment, indicating that the third manganese ion, contributes to reposition the flap, but is dispensable for catalysis., Studies of metal binding to MspP using isothermal titration calorimetry, revealed that the three Mn(2+)-binding sites display distinct affinities, with dissociation constants in the nano- and micromolar range for the two, catalytic metal ions and a significantly lower affinity for the third, metal-binding site. In agreement, the structure of inactive MspP at acidic, pH was determined at atomic resolution and shown to lack the third metal, ion in the active site. Structural comparisons of all bacterial, phosphatases revealed positional variations in the third metal-binding, site that are correlated with the presence of bound substrate and the, conformation of the flap segment, supporting a role of this metal ion in, assisting enzyme-substrate interactions. | |||
==About this Structure== | ==About this Structure== | ||
2CM1 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 MN and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phosphoprotein_phosphatase Phosphoprotein phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.16 3.1.3.16] | 2CM1 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 MN and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phosphoprotein_phosphatase Phosphoprotein phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.16 3.1.3.16] Known structural/functional Sites: <scene name='pdbsite=AC1:Mn Binding Site For Chain A'>AC1</scene>, <scene name='pdbsite=AC2:Mn Binding Site For Chain A'>AC2</scene> and <scene name='pdbsite=AC3:Gol Binding Site For Chain A'>AC3</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2CM1 OCA]. | ||
==Reference== | |||
Structural and Binding Studies of the Three-metal Center in Two Mycobacterial PPM Ser/Thr Protein Phosphatases., Wehenkel A, Bellinzoni M, Schaeffer F, Villarino A, Alzari PM, J Mol Biol. 2007 Dec 7;374(4):890-8. Epub 2007 Oct 2. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17961594 17961594] | |||
[[Category: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Phosphoprotein phosphatase]] | [[Category: Phosphoprotein phosphatase]] | ||
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[[Category: ser/thr protein phosphatase pstp]] | [[Category: ser/thr protein phosphatase pstp]] | ||
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