1t5d

[[Image:1t5d.gif|left|200px]]<br /><applet load="1t5d" size="350" color="white" frame="true" align="right" spinBox="true"

caption="1t5d, resolution 2.206&Aring;" />

'''4-Chlorobenzoyl-CoA Ligase/Synthetase bound to 4-chlorobenzoate'''<br />

==Overview==

4-Chlorobenzoate:CoA ligase (CBAL) is a member of a family of adenylate-forming enzymes that catalyze two-step adenylation and thioester-forming reactions. In previous studies, we have provided structural evidence that members of this enzyme family (exemplified by acetyl-CoA synthetase) use a large domain rotation to catalyze the respective partial reactions [A. M. Gulick, V. J. Starai, A. R. Horswill, K. M. Homick, and J. C. Escalante-Semerena, (2003) Biochemistry 42, 2866-2873]. CBAL catalyzes the synthesis of 4-chlorobenzoyl-CoA, the first step in the 4-chlorobenzoate degredation pathway in PCB-degrading bacteria. We have solved the 2.0 A crystal structure of the CBAL enzyme from Alcaligenes sp. AL3007 using multiwavelength anomalous dispersion. The results demonstrate that in the absence of any ligands, or bound to the aryl substrate 4-chlorobenzoate, the enzyme adopts the conformation poised for catalysis of the adenylate-forming half-reaction. We hypothesize that coenzyme A binding is required for stabilization of the alternate conformation, which catalyzes the 4-CBA-CoA thioester-forming reaction. We have also determined the structure of the enzyme bound to the aryl substrate 4-chlorobenzoate. The aryl binding pocket is composed of Phe184, His207, Val208, Val209, Phe249, Ala280, Ile303, Gly305, Met310, and Asn311. The structure of the 4-chlorobenzoate binding site is discussed in the context of the binding sites of other family members to gain insight into substrate specificity and evolution of new function.

 

==About this Structure==

1T5D is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Alcaligenes_sp._al3007 Alcaligenes sp. al3007] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=174:'>174</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/4-chlorobenzoate--CoA_ligase 4-chlorobenzoate--CoA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.2.1.33 6.2.1.33] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T5D OCA].

 

==Reference==

Crystal structure of 4-chlorobenzoate:CoA ligase/synthetase in the unliganded and aryl substrate-bound states., Gulick AM, Lu X, Dunaway-Mariano D, Biochemistry. 2004 Jul 13;43(27):8670-9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15236575 15236575]

[[Category: 4-chlorobenzoate--CoA ligase]]

[[Category: Alcaligenes sp. al3007]]

[[Category: Single protein]]

[[Category: Dunaway-Mariano, D.]]

[[Category: Gulick, A M.]]

[[Category: Lu, X.]]