1gbm: Difference between revisions
New page: left|200px<br /><applet load="1gbm" size="450" color="white" frame="true" align="right" spinBox="true" caption="1gbm, resolution 2.28Å" /> '''ALPHA-LYTIC PROTEASE... |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1gbm.jpg|left|200px]]<br /><applet load="1gbm" size=" | [[Image:1gbm.jpg|left|200px]]<br /><applet load="1gbm" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1gbm, resolution 2.28Å" /> | caption="1gbm, resolution 2.28Å" /> | ||
'''ALPHA-LYTIC PROTEASE WITH MET 190 REPLACED BY ALA COMPLEX WITH METHOXYSUCCINYL-ALA-ALA-PRO-PHENYLALANINE BORONIC ACID'''<br /> | '''ALPHA-LYTIC PROTEASE WITH MET 190 REPLACED BY ALA COMPLEX WITH METHOXYSUCCINYL-ALA-ALA-PRO-PHENYLALANINE BORONIC ACID'''<br /> | ||
==Overview== | ==Overview== | ||
Gly216 in the active site of the broadly specific MA190 mutant of | Gly216 in the active site of the broadly specific MA190 mutant of alpha-lytic protease has been found to be remarkably tolerant of amino acid substitutions. Side-chains as large as Trp can be accommodated within the substrate-binding pocket without abolishing catalysis, and have major effects upon the substrate specificity of the enzyme. Kinetic characterization of eleven enzymatically active mutants against a panel of eight substrates clearly revealed the functional consequences of the substitutions at position 216. To understand better the structural basis for their altered specificity, the GA216 + MA190 and GL216 + MA190 mutants have been crystallized both with and without a representative series of peptide boronic acid transition-state analog inhibitors. An empirical description and non-parametric statistical analysis of structural variation among these enzyme: inhibitor complexes is presented. The roles of active site plasticity and dynamics in alpha-lytic protease function and substrate preference are also addressed. The results strongly suggest that substrate specificity determination in alpha-lytic protease is a distributed property of the active site and substrate molecule. | ||
==About this Structure== | ==About this Structure== | ||
1GBM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Lysobacter_enzymogenes Lysobacter enzymogenes] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. This structure | 1GBM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Lysobacter_enzymogenes Lysobacter enzymogenes] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. This structure supersedes the now removed PDB entry 1P08. Active as [http://en.wikipedia.org/wiki/Alpha-lytic_endopeptidase Alpha-lytic endopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.12 3.4.21.12] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GBM OCA]. | ||
==Reference== | ==Reference== | ||
| Line 14: | Line 14: | ||
[[Category: Lysobacter enzymogenes]] | [[Category: Lysobacter enzymogenes]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Agard, D | [[Category: Agard, D A.]] | ||
[[Category: Mace, J | [[Category: Mace, J E.]] | ||
[[Category: SO4]] | [[Category: SO4]] | ||
[[Category: active-site mutation]] | [[Category: active-site mutation]] | ||
[[Category: inhibitor complex]] | [[Category: inhibitor complex]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:48:23 2008'' | ||
Revision as of 13:48, 21 February 2008
|
ALPHA-LYTIC PROTEASE WITH MET 190 REPLACED BY ALA COMPLEX WITH METHOXYSUCCINYL-ALA-ALA-PRO-PHENYLALANINE BORONIC ACID
OverviewOverview
Gly216 in the active site of the broadly specific MA190 mutant of alpha-lytic protease has been found to be remarkably tolerant of amino acid substitutions. Side-chains as large as Trp can be accommodated within the substrate-binding pocket without abolishing catalysis, and have major effects upon the substrate specificity of the enzyme. Kinetic characterization of eleven enzymatically active mutants against a panel of eight substrates clearly revealed the functional consequences of the substitutions at position 216. To understand better the structural basis for their altered specificity, the GA216 + MA190 and GL216 + MA190 mutants have been crystallized both with and without a representative series of peptide boronic acid transition-state analog inhibitors. An empirical description and non-parametric statistical analysis of structural variation among these enzyme: inhibitor complexes is presented. The roles of active site plasticity and dynamics in alpha-lytic protease function and substrate preference are also addressed. The results strongly suggest that substrate specificity determination in alpha-lytic protease is a distributed property of the active site and substrate molecule.
About this StructureAbout this Structure
1GBM is a Single protein structure of sequence from Lysobacter enzymogenes with as ligand. This structure supersedes the now removed PDB entry 1P08. Active as Alpha-lytic endopeptidase, with EC number 3.4.21.12 Full crystallographic information is available from OCA.
ReferenceReference
Kinetic and structural characterization of mutations of glycine 216 in alpha-lytic protease: a new target for engineering substrate specificity., Mace JE, Agard DA, J Mol Biol. 1995 Dec 8;254(4):720-36. PMID:7500345
Page seeded by OCA on Thu Feb 21 12:48:23 2008