1twi: Difference between revisions

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New page: left|200px<br /><applet load="1twi" size="450" color="white" frame="true" align="right" spinBox="true" caption="1twi, resolution 2.00Å" /> '''Crystal structure of...
 
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[[Image:1twi.gif|left|200px]]<br /><applet load="1twi" size="450" color="white" frame="true" align="right" spinBox="true"  
[[Image:1twi.gif|left|200px]]<br /><applet load="1twi" size="350" color="white" frame="true" align="right" spinBox="true"  
caption="1twi, resolution 2.00&Aring;" />
caption="1twi, resolution 2.00&Aring;" />
'''Crystal structure of Diaminopimelate Decarboxylase from m. jannaschii in co-complex with L-lysine'''<br />
'''Crystal structure of Diaminopimelate Decarboxylase from m. jannaschii in co-complex with L-lysine'''<br />


==Overview==
==Overview==
Cocrystal structures of Methanococcus jannaschii diaminopimelate, decarboxylase (DAPDC) bound to a substrate analog, azelaic acid, and its, L-lysine product have been determined at 2.6 A and 2.0 A, respectively., This PLP-dependent enzyme is responsible for the final step of L-lysine, biosynthesis in bacteria and plays a role in beta-lactam antibiotic, resistance in Staphylococcus aureus. Substrate specificity derives from, recognition of the L-chiral center of diaminopimelate and a system of, ionic "molecular rulers" that dictate substrate length. A coupled-enzyme, assay system permitted measurement of kinetic parameters for recombinant, DAPDCs and inhibition constants (K(i)) for azelaic acid (89 microM) and, other substrate analogs. Implications for rational design of, broad-spectrum antimicrobial agents targeted against DAPDCs of, drug-resistant strains of bacterial pathogens, such as Staphylococcus, aureus, are discussed.
Cocrystal structures of Methanococcus jannaschii diaminopimelate decarboxylase (DAPDC) bound to a substrate analog, azelaic acid, and its L-lysine product have been determined at 2.6 A and 2.0 A, respectively. This PLP-dependent enzyme is responsible for the final step of L-lysine biosynthesis in bacteria and plays a role in beta-lactam antibiotic resistance in Staphylococcus aureus. Substrate specificity derives from recognition of the L-chiral center of diaminopimelate and a system of ionic "molecular rulers" that dictate substrate length. A coupled-enzyme assay system permitted measurement of kinetic parameters for recombinant DAPDCs and inhibition constants (K(i)) for azelaic acid (89 microM) and other substrate analogs. Implications for rational design of broad-spectrum antimicrobial agents targeted against DAPDCs of drug-resistant strains of bacterial pathogens, such as Staphylococcus aureus, are discussed.


==About this Structure==
==About this Structure==
1TWI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Methanocaldococcus_jannaschii Methanocaldococcus jannaschii] with MG, LYS and PLP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Diaminopimelate_decarboxylase Diaminopimelate decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.20 4.1.1.20] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1TWI OCA].  
1TWI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Methanocaldococcus_jannaschii Methanocaldococcus jannaschii] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=LYS:'>LYS</scene> and <scene name='pdbligand=PLP:'>PLP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Diaminopimelate_decarboxylase Diaminopimelate decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.20 4.1.1.20] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TWI OCA].  


==Reference==
==Reference==
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[[Category: Methanocaldococcus jannaschii]]
[[Category: Methanocaldococcus jannaschii]]
[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Bonanno, J.B.]]
[[Category: Bonanno, J B.]]
[[Category: Burley, S.K.]]
[[Category: Burley, S K.]]
[[Category: He, G.]]
[[Category: He, G.]]
[[Category: Lencastre, H.De.]]
[[Category: Lencastre, H De.]]
[[Category: NYSGXRC, New.York.Structural.GenomiX.Research.Consortium.]]
[[Category: NYSGXRC, New York Structural GenomiX Research Consortium.]]
[[Category: Pinho, M.G.]]
[[Category: Pinho, M G.]]
[[Category: Rajashankar, K.R.]]
[[Category: Rajashankar, K R.]]
[[Category: Ray, S.S.]]
[[Category: Ray, S S.]]
[[Category: Tomasz, A.]]
[[Category: Tomasz, A.]]
[[Category: LYS]]
[[Category: LYS]]
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[[Category: t135]]
[[Category: t135]]


''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 03:39:15 2007''
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:18:05 2008''

Revision as of 16:18, 21 February 2008

File:1twi.gif


1twi, resolution 2.00Å

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Crystal structure of Diaminopimelate Decarboxylase from m. jannaschii in co-complex with L-lysine

OverviewOverview

Cocrystal structures of Methanococcus jannaschii diaminopimelate decarboxylase (DAPDC) bound to a substrate analog, azelaic acid, and its L-lysine product have been determined at 2.6 A and 2.0 A, respectively. This PLP-dependent enzyme is responsible for the final step of L-lysine biosynthesis in bacteria and plays a role in beta-lactam antibiotic resistance in Staphylococcus aureus. Substrate specificity derives from recognition of the L-chiral center of diaminopimelate and a system of ionic "molecular rulers" that dictate substrate length. A coupled-enzyme assay system permitted measurement of kinetic parameters for recombinant DAPDCs and inhibition constants (K(i)) for azelaic acid (89 microM) and other substrate analogs. Implications for rational design of broad-spectrum antimicrobial agents targeted against DAPDCs of drug-resistant strains of bacterial pathogens, such as Staphylococcus aureus, are discussed.

About this StructureAbout this Structure

1TWI is a Single protein structure of sequence from Methanocaldococcus jannaschii with , and as ligands. Active as Diaminopimelate decarboxylase, with EC number 4.1.1.20 Full crystallographic information is available from OCA.

ReferenceReference

Cocrystal structures of diaminopimelate decarboxylase: mechanism, evolution, and inhibition of an antibiotic resistance accessory factor., Ray SS, Bonanno JB, Rajashankar KR, Pinho MG, He G, De Lencastre H, Tomasz A, Burley SK, Structure. 2002 Nov;10(11):1499-508. PMID:12429091

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