1tlp
From Proteopedia
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| - | [[Image:1tlp.gif|left|200px]] | + | [[Image:1tlp.gif|left|200px]] |
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| - | '''CRYSTALLOGRAPHIC STRUCTURAL ANALYSIS OF PHOSPHORAMIDATES AS INHIBITORS AND TRANSITION-STATE ANALOGS OF THERMOLYSIN''' | + | {{Structure |
| + | |PDB= 1tlp |SIZE=350|CAPTION= <scene name='initialview01'>1tlp</scene>, resolution 2.3Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=RHA:6-DEOXY-MANNOSE-1'-PHOSPHATE'>RHA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> and <scene name='pdbligand=ZN:ZINC ION'>ZN</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Thermolysin Thermolysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.27 3.4.24.27] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''CRYSTALLOGRAPHIC STRUCTURAL ANALYSIS OF PHOSPHORAMIDATES AS INHIBITORS AND TRANSITION-STATE ANALOGS OF THERMOLYSIN''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1TLP is a [ | + | 1TLP is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TLP OCA]. |
==Reference== | ==Reference== | ||
| - | Crystallographic structural analysis of phosphoramidates as inhibitors and transition-state analogs of thermolysin., Tronrud DE, Monzingo AF, Matthews BW, Eur J Biochem. 1986 Jun 2;157(2):261-8. PMID:[http:// | + | Crystallographic structural analysis of phosphoramidates as inhibitors and transition-state analogs of thermolysin., Tronrud DE, Monzingo AF, Matthews BW, Eur J Biochem. 1986 Jun 2;157(2):261-8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/3709536 3709536] |
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Thermolysin]] | [[Category: Thermolysin]] | ||
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[[Category: hydrolase (metalloproteinase)]] | [[Category: hydrolase (metalloproteinase)]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:20:02 2008'' |
Revision as of 12:20, 20 March 2008
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| , resolution 2.3Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , and | ||||||
| Activity: | Thermolysin, with EC number 3.4.24.27 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTALLOGRAPHIC STRUCTURAL ANALYSIS OF PHOSPHORAMIDATES AS INHIBITORS AND TRANSITION-STATE ANALOGS OF THERMOLYSIN
Overview
The mode of binding to thermolysin of the unsubstituted phosphoramidate inhibitor N-phosphoryl-L-leucinamide (P-Leu-NH2) has been determined crystallographically and refined at high resolution (R = 17.9% to 0.16-nm resolution). The mode of binding of the naturally occurring thermolysin inhibitor phosphoramidon reported previously [Weaver, L. H., Kester, W. R. and Matthews, B. W. (1977) J. Mol. Biol. 114, 119-132] has also been confirmed by crystallographic refinement (R = 17.4% to 0.23-nm resolution). Phosphoramidon binds to the enzyme with a single oxygen of the phosphoramidate moiety as a zinc ligand. Together with three ligands to the metal from the protein the resultant complex has approximately tetrahedral geometry. However, in the case of P-Leu-NH2, two of the phosphoramidate oxygens interact with the zinc to form a complex that tends towards pentacoordinate. In this respect, P-Leu-NH2 appears to be a better transition-state analog than is phosphoramidon. In addition, the phosphorus-nitrogen bond length in P-Leu-NH2 is 0.18 nm, suggesting that the nitrogen is protonated whereas the same bond in phosphoramidon is much shorter (0.15 nm) suggesting that the nitrogen does not carry a charge. In phosphoramidon the distance from the phosphoramide nitrogen to Glu-143 is 0.39 nm whereas in P-Leu-NH2 this distance decreases to 0.34 nm. Taken together, these observations provide additional evidence in support of the participation of pentacoordinate intermediates in the mechanism of action of thermolysin [Holmes, M. A. and Matthews, B. W. (1981) Biochemistry 20, 6912-6920] and the role of Glu-143 in first promoting the attack of a water molecule on the carbonyl carbon of the scissile bond and subsequently acting as a 'proton shuttle' to transfer the proton to the leaving nitrogen [Monzingo, A. F. and Matthews, B. W. (1984) Biochemistry 23, 5724-5729; Hangauer, D. G., Monzingo, A. F. and Matthews, B. W. (1984) Biochemistry 23, 5730-5741].
About this Structure
1TLP is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
Reference
Crystallographic structural analysis of phosphoramidates as inhibitors and transition-state analogs of thermolysin., Tronrud DE, Monzingo AF, Matthews BW, Eur J Biochem. 1986 Jun 2;157(2):261-8. PMID:3709536
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