2r5v
From Proteopedia
Hydroxymandelate Synthase Crystal Structure
Structural highlights
Function[HMAS_AMYOR] Required to synthesize hydroxyphenylglycine, a recurring skeletal component of nonproteinogenic macrocyclic peptide antibiotics such as vancomycin. Catalyzes the conversion of p-hydroxyphenylpyruvate to p-hydroxymandelate. The decarboxylation and hydroxylation activities of HmaS show novel and distinct regioselectivity, compared to all other known p-hydroxyphenylpyruvate dioxygenases, by hydroxylating the benzylic position of the substrate instead of the phenyl ring.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe crystal structure of the hydroxymandelate synthase (HMS).Co2+.hydroxymandelate (HMA) complex determined to a resolution of 2.3 A reveals an overall fold that consists of two similar beta-barrel domains, one of which contains the characteristic His/His/acid metal-coordination motif (facial triad) found in the majority of Fe2+-dependent oxygenases. The fold of the alpha-carbon backbone closely resembles that of the evolutionarily related enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD) in its closed conformation with a root-mean-square deviation of 1.85 A. HPPD uses the same substrates as HMS but forms instead homogentisate (HG). The active site of HMS is significantly smaller than that observed in HPPD, reflecting the relative changes in shape that occur in the conversion of the common HPP substrate to the respective HMA or HG products. The HMA benzylic hydroxyl and carboxylate oxygens coordinate to the Co2+ ion, and three other potential H-bonding interactions to active site residue side chains are observed. Additionally, it is noted that there is a buried well-ordered water molecule 3.2 A from the distal carboxylate oxygen. The p-hydroxyl group of HMA is within hydrogen-bonding distance of the side chain hydroxyl of a serine residue (Ser201) that is conserved in both HMS and HPPD. This potential hydrogen bond and the known geometry of iron ligation for the substrate allowed us to model 4-hydroxyphenylpyruvate (HPP) in the active sites of both HMS and HPPD. These models suggest that the position of the HPP substrate differs between the two enzymes. In HMS, HPP binds analogously to HMA, while in HPPD, the p-hydroxyl group of HPP acts as a hydrogen-bond donor and acceptor to Ser201 and Asn216, respectively. It is suggested that this difference in the ring orientation of the substrate and the corresponding intermediates influences the site of hydroxylation. Two roads diverged: the structure of hydroxymandelate synthase from Amycolatopsis orientalis in complex with 4-hydroxymandelate.,Brownlee J, He P, Moran GR, Harrison DH Biochemistry. 2008 Feb 19;47(7):2002-13. Epub 2008 Jan 24. PMID:18215022[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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