1xvv
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(New page: 200px<br /><applet load="1xvv" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xvv, resolution 2.40Å" /> '''Crystal Structure of...) |
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| - | [[Image:1xvv.gif|left|200px]]<br /><applet load="1xvv" size=" | + | [[Image:1xvv.gif|left|200px]]<br /><applet load="1xvv" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1xvv, resolution 2.40Å" /> | caption="1xvv, resolution 2.40Å" /> | ||
'''Crystal Structure of CaiB mutant D169A in complex with carnitinyl-CoA'''<br /> | '''Crystal Structure of CaiB mutant D169A in complex with carnitinyl-CoA'''<br /> | ||
==Overview== | ==Overview== | ||
| - | L-Carnitine (R-[-]-3-hydroxy-4-trimethylaminobutyrate) is found in both | + | L-Carnitine (R-[-]-3-hydroxy-4-trimethylaminobutyrate) is found in both eukaryotic and prokaryotic cells and participates in diverse processes including long-chain fatty-acid transport and osmoprotection. The enzyme crotonobetainyl/gamma-butyrobetainyl-CoA:carnitine CoA-transferase (CaiB; E.C. 2.8.3.-) catalyzes the first step in carnitine metabolism, leading to the final product gamma-butyrobetaine. The crystal structures of Escherichia coli apo-CaiB, as well as its Asp169Ala mutant bound to CoA and to carnitinyl-CoA, have been determined and refined to 1.6, 2.4, and 2.4 A resolution, respectively. CaiB is composed of two identical circular chains that together form an intertwined dimer. Each monomer consists of a large domain, containing a Rossmann fold, and a small domain. The monomer and dimer resemble those of formyl-CoA transferase from Oxalobacter formigenes, as well as E. coli YfdW, a putative type-III CoA transferase of unknown function. The CoA cofactor-binding site is formed at the interface of the large domain of one monomer and the small domain from the second monomer. Most of the protein-CoA interactions are formed with the Rossmann fold domain. While the location of cofactor binding is similar in the three proteins, the specific CoA-protein interactions vary somewhat between CaiB, formyl-CoA transferase, and YfdW. CoA binding results in a change in the relative positions of the large and small domains compared with apo-CaiB. The observed carnitinyl-CoA product in crystals of the CaiB Asp169Ala mutant cocrystallized with crotonoyl-CoA and carnitine could result from (i) a catalytic mechanism involving a ternary enzyme-substrate complex, independent of a covalent anhydride intermediate with Asp169, (ii) a spontaneous reaction of the substrates in solution, followed by binding to the enzyme, or (iii) an involvement of another residue substituting functionally for Asp169, such as Glu23. |
==About this Structure== | ==About this Structure== | ||
| - | 1XVV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with CCQ as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1XVV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=CCQ:'>CCQ</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XVV OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Li, Y.]] | [[Category: Li, Y.]] | ||
[[Category: Matte, A.]] | [[Category: Matte, A.]] | ||
| - | [[Category: Rangarajan, E | + | [[Category: Rangarajan, E S.]] |
[[Category: CCQ]] | [[Category: CCQ]] | ||
[[Category: asp mutant]] | [[Category: asp mutant]] | ||
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[[Category: coa-transferase]] | [[Category: coa-transferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:59:12 2008'' |
Revision as of 13:59, 21 February 2008
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Crystal Structure of CaiB mutant D169A in complex with carnitinyl-CoA
Overview
L-Carnitine (R-[-]-3-hydroxy-4-trimethylaminobutyrate) is found in both eukaryotic and prokaryotic cells and participates in diverse processes including long-chain fatty-acid transport and osmoprotection. The enzyme crotonobetainyl/gamma-butyrobetainyl-CoA:carnitine CoA-transferase (CaiB; E.C. 2.8.3.-) catalyzes the first step in carnitine metabolism, leading to the final product gamma-butyrobetaine. The crystal structures of Escherichia coli apo-CaiB, as well as its Asp169Ala mutant bound to CoA and to carnitinyl-CoA, have been determined and refined to 1.6, 2.4, and 2.4 A resolution, respectively. CaiB is composed of two identical circular chains that together form an intertwined dimer. Each monomer consists of a large domain, containing a Rossmann fold, and a small domain. The monomer and dimer resemble those of formyl-CoA transferase from Oxalobacter formigenes, as well as E. coli YfdW, a putative type-III CoA transferase of unknown function. The CoA cofactor-binding site is formed at the interface of the large domain of one monomer and the small domain from the second monomer. Most of the protein-CoA interactions are formed with the Rossmann fold domain. While the location of cofactor binding is similar in the three proteins, the specific CoA-protein interactions vary somewhat between CaiB, formyl-CoA transferase, and YfdW. CoA binding results in a change in the relative positions of the large and small domains compared with apo-CaiB. The observed carnitinyl-CoA product in crystals of the CaiB Asp169Ala mutant cocrystallized with crotonoyl-CoA and carnitine could result from (i) a catalytic mechanism involving a ternary enzyme-substrate complex, independent of a covalent anhydride intermediate with Asp169, (ii) a spontaneous reaction of the substrates in solution, followed by binding to the enzyme, or (iii) an involvement of another residue substituting functionally for Asp169, such as Glu23.
About this Structure
1XVV is a Single protein structure of sequence from Escherichia coli with as ligand. Full crystallographic information is available from OCA.
Reference
Crystal structure of Escherichia coli crotonobetainyl-CoA: carnitine CoA-transferase (CaiB) and its complexes with CoA and carnitinyl-CoA., Rangarajan ES, Li Y, Iannuzzi P, Cygler M, Matte A, Biochemistry. 2005 Apr 19;44(15):5728-38. PMID:15823031
Page seeded by OCA on Thu Feb 21 15:59:12 2008
Categories: Escherichia coli | Single protein | Cygler, M. | Iannuzzi, P. | Li, Y. | Matte, A. | Rangarajan, E S. | CCQ | Asp mutant | Caib | Carnityl-coa | Coa-transferase
