Editing Aspartate transaminase (section)

== Structure ==
[[File:Gallus gallus aspartate aminotransferase dimer.png|thumb|449x449px|Structure of the aspartate transaminase dimer from chicken heart mitochondria. The large and small domains are coloured blue and red, respectively with the N-terminal residues highlighted in green. {{PDB|7AAT}}]]
[[X-ray crystallography]] studies have been performed to determine the structure of aspartate transaminase from various sources, including chicken mitochondria,<ref name="pmid1593633">{{Cite journal |vauthors=McPhalen CA, Vincent MG, Jansonius JN |date=May 1992 |title=X-ray structure refinement and comparison of three forms of mitochondrial aspartate aminotransferase |journal=Journal of Molecular Biology |volume=225 |issue=2 |pages=495–517 |doi=10.1016/0022-2836(92)90935-D |pmid=1593633}}</ref> pig heart cytosol,<ref name="pmid9211866">{{Cite journal |vauthors=Rhee S, Silva MM, Hyde CC, Rogers PH, Metzler CM, Metzler DE, Arnone A |date=July 1997 |title=Refinement and comparisons of the crystal structures of pig cytosolic aspartate aminotransferase and its complex with 2-methylaspartate |journal=The Journal of Biological Chemistry |volume=272 |issue=28 |pages=17293–17302 |doi=10.1074/jbc.272.28.17293 |pmid=9211866 |doi-access=free}}</ref> and ''E. coli''.<ref name="pmid3071527">{{Cite journal |display-authors=6 |vauthors=Kamitori S, Hirotsu K, Higuchi T, Kondo K, Inoue K, Kuramitsu S, Kagamiyama H, Higuchi Y, Yasuoka N, Kusunoki M |date=September 1988 |title=Three-dimensional structure of aspartate aminotransferase from Escherichia coli at 2.8 A resolution |journal=Journal of Biochemistry |volume=104 |issue=3 |pages=317–318 |doi=10.1093/oxfordjournals.jbchem.a122464 |pmid=3071527}}</ref><ref name="pmid1993208">{{Cite journal |vauthors=Danishefsky AT, Onnufer JJ, Petsko GA, Ringe D |date=February 1991 |title=Activity and structure of the active-site mutants R386Y and R386F of Escherichia coli aspartate aminotransferase |journal=Biochemistry |volume=30 |issue=7 |pages=1980–1985 |doi=10.1021/bi00221a035 |pmid=1993208}}</ref>  Overall, the three-dimensional polypeptide structure for all species is quite similar.  AST is [[Protein dimer|dimeric]], consisting of two identical subunits, each with approximately 400 amino acid residues and a molecular weight of approximately 45 kD.<ref name="pmid2197992" />  Each subunit is composed of a large and a small domain, as well as a third domain consisting of the N-terminal residues 3-14; these few residues form a strand, which links and stabilizes the two subunits of the dimer.  The large domain, which includes residues 48-325, binds the PLP cofactor via an [[aldimine]] linkage to the ε-amino group of Lys258.  Other residues in this domain – Asp 222 and Tyr 225 – also interact with PLP via [[hydrogen bonding]].  The small domain consists of residues 15-47 and 326-410 and represents a flexible region that shifts the enzyme from an "open" to a "closed" conformation upon substrate binding.<ref name="pmid1593633" /><ref name="pmid1993208" /><ref name="pmid1522585">{{Cite journal |vauthors=McPhalen CA, Vincent MG, Picot D, Jansonius JN, Lesk AM, Chothia C |date=September 1992 |title=Domain closure in mitochondrial aspartate aminotransferase |journal=Journal of Molecular Biology |volume=227 |issue=1 |pages=197–213 |doi=10.1016/0022-2836(92)90691-C |pmid=1522585}}</ref>

The two independent active sites are positioned near the interface between the two domains. Within each active site, a couple arginine residues are responsible for the enzyme's specificity for [[dicarboxylic acid]] substrates:  Arg386 interacts with the substrate's proximal (α-)carboxylate group, while Arg292 complexes with the distal (side-chain) carboxylate.<ref name="pmid1593633" /><ref name="pmid1993208" />

In terms of secondary structure, AST contains both α and β elements.  Each domain has a central sheet of β-strands with α-helices packed on either side.{{cn|date=November 2021}}