|
|
| Line 1: |
Line 1: |
| [[Image:1tz2.gif|left|200px]] | | {{Seed}} |
| | [[Image:1tz2.png|left|200px]] |
|
| |
|
| <!-- | | <!-- |
| Line 9: |
Line 10: |
| {{STRUCTURE_1tz2| PDB=1tz2 | SCENE= }} | | {{STRUCTURE_1tz2| PDB=1tz2 | SCENE= }} |
|
| |
|
| '''Crystal structure of 1-aminocyclopropane-1-carboyxlate deaminase complexed with ACC'''
| | ===Crystal structure of 1-aminocyclopropane-1-carboyxlate deaminase complexed with ACC=== |
|
| |
|
|
| |
|
| ==Overview==
| | <!-- |
| 1-Aminocyclopropane-1-carboxylate (ACC) deaminase is a pyridoxal 5'-phosphate (PLP) dependent enzyme catalyzing the opening of the cyclopropane ring of ACC to give alpha-ketobutyric acid and ammonia as the products. This ring cleavage reaction is unusual because the substrate, ACC, contains no abstractable alpha-proton and the carboxyl group is retained in the product. How the reaction is initiated to generate an alpha-carbanionic intermediate, which is the common entry for most PLP-dependent reactions, is not obvious. To gain insight into this unusual ring-opening reaction, we have solved the crystal structures of ACC deaminase from Pseudomonas sp. ACP in complex with substrate ACC, an inhibitor, 1-aminocyclopropane-1-phosphonate (ACP), the product alpha-ketobutyrate, and two d-amino acids. Several notable observations of these structural studies include the following: (1) a typically elusive gem-diamine intermediate is trapped in the enzyme complex with ACC or ACP; (2) Tyr294 is in close proximity (3.0 A) to the pro-S methylene carbon of ACC in the gem-diamine complexes, implicating a direct role of this residue in the ring-opening reaction; (3) Tyr294 may also be responsible for the abstraction of the alpha-proton from d-amino acids, a prelude to the subsequent deamination reaction; (4) the steric hindrance precludes accessibility of active site functional groups to the l-amino acid substrates and may account for the stereospecificity of this enzyme toward d-amino acids. These structural data provide evidence favoring a mechanism in which the ring cleavage is induced by a nucleophilic attack at the pro-S beta-methylene carbon of ACC, with Tyr294 as the nucleophile. However, these observations are also consistent with an alternative mechanistic possibility in which the ring opening is acid-catalyzed and may be facilitated by charge relay through PLP, where Tyr294 functions as a general acid. The results of mutagenesis studies corroborated the assigned critical role for Tyr294 in the catalysis.
| | The line below this paragraph, {{ABSTRACT_PUBMED_15491139}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 15491139 is the PubMed ID number. |
| | --> |
| | {{ABSTRACT_PUBMED_15491139}} |
|
| |
|
| ==About this Structure== | | ==About this Structure== |
| Line 38: |
Line 42: |
| [[Category: Structure]] | | [[Category: Structure]] |
| [[Category: Substrate]] | | [[Category: Substrate]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 10:32:32 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 12:30:17 2008'' |