1pwh
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(New page: 200px<br /><applet load="1pwh" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pwh, resolution 2.60Å" /> '''Rat Liver L-Serine D...)
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Revision as of 22:03, 20 November 2007
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Rat Liver L-Serine Dehydratase- Complex with PYRIDOXYL-(O-METHYL-SERINE)-5-MONOPHOSPHATE
Overview
SDH (L-serine dehydratase, EC 4.3.1.17) catalyzes the pyridoxal, 5'-phosphate (PLP)-dependent dehydration of L-serine to yield pyruvate and, ammonia. Liver SDH plays an important role in gluconeogenesis. Formation, of pyruvate by SDH is a two-step reaction in which the hydroxyl group of, serine is cleaved to produce aminoacrylate, and then the aminoacrylate is, deaminated by nonenzymatic hydrolysis to produce pyruvate. The crystal, structure of rat liver apo-SDH was determined by single isomorphous, replacement at 2.8 A resolution. The holo-SDH crystallized with, O-methylserine (OMS) was also determined at 2.6 A resolution by molecular, replacement. SDH is composed of two domains, and each domain has a typical, alphabeta-open structure. The active site is located in the cleft between, the two domains. The holo-SDH contained PLP-OMS aldimine in the active, site, indicating that OMS can form the Schiff base linkage with PLP, but, the subsequent dehydration did not occur. Apo-SDH forms a dimer by, inserting the small domain into the catalytic cleft of the partner subunit, so that the active site is closed. Holo-SDH also forms a dimer by making, contacts at the back of the clefts so that the dimerization does not close, the catalytic cleft. The phosphate group of PLP is surrounded by a, characteristic G-rich sequence ((168)GGGGL(172)) and forms hydrogen bonds, with the amide groups of those amino acid residues, suggesting that the, phosphate group can be protonated. N(1) of PLP participates in a hydrogen, bond with Cys303, and similar hydrogen bonds with N(1) participating are, seen in other beta-elimination enzymes. These hydrogen bonding schemes, indicate that N(1) is not protonated, and thus, the pyridine ring cannot, take a quinone-like structure. These characteristics of the bound PLP, suggest that SDH catalysis is not facilitated by forming the, resonance-stabilized structure of the PLP-Ser aldimine as seen in, aminotransferases. A possible catalytic mechanism involves the phosphate, group, surrounded by the characteristic sequence, acting as a general acid, to donate a proton to the leaving hydroxyl group of serine.
About this Structure
1PWH is a Single protein structure of sequence from Rattus norvegicus with K and PLV as ligands. Active as L-serine ammonia-lyase, with EC number 4.3.1.17 Full crystallographic information is available from OCA.
Reference
Crystal structure of serine dehydratase from rat liver., Yamada T, Komoto J, Takata Y, Ogawa H, Pitot HC, Takusagawa F, Biochemistry. 2003 Nov 11;42(44):12854-65. PMID:14596599
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