PDBsum entry 3l6c

Isomerase

PDB id: 3l6c

Contents

Protein chains

322 a.a. *

Ligands

PLP ×2

MLI ×2

Metals

_MN ×2

Waters ×80

* Residue conservation analysis

PDB id:

3l6c

Name:

Isomerase

Title:

X-ray crystal structure of rat serine racemase in complex with malonate a potent inhibitor

Structure:

Serine racemase. Chain: a, b. Engineered: yes. Mutation: yes

Source:

Rattus norvegicus. Rat. Organism_taxid: 10116. Gene: srr. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.20Å R-factor: 0.219 R-free: 0.267

Authors:

M.A.Smith,V.Mack,A.Ebneth,I.Moraes,B.Felicetti,M.Wood,D.Schonfeld, O.Mather,A.Cesura,J.Barker

Key ref:

M.A.Smith et al. (2010). The structure of mammalian serine racemase: evidence for conformational changes upon inhibitor binding. J Biol Chem, 285, 12873-12881. PubMed id: 20106978

Date:

23-Dec-09 Release date: 26-Jan-10

Protein chains

Q76EQ0  (SRR_RAT) -  Serine racemase from Rattus norvegicus

Seq: 333 a.a.

Struc: 322 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: E.C.4.3.1.17 - L-serine ammonia-lyase.
• Reaction: L-serine = pyruvate + NH4⁺

L-serine (Bound ligand (Het Group name = MLI) matches with 75.00% similarity) = pyruvate + NH4(+)

• Cofactor: Pyridoxal 5'-phosphate or iron-sulfur

Pyridoxal 5'-phosphate (Bound ligand (Het Group name = PLP) matches with 93.75% similarity) or iron-sulfur

• Enzyme class 2: E.C.4.3.1.18 - D-serine ammonia-lyase.
• Reaction: D-serine = pyruvate + NH4⁺

D-serine (Bound ligand (Het Group name = MLI) matches with 75.00% similarity) = pyruvate + NH4(+)

• Cofactor: Pyridoxal 5'-phosphate

Pyridoxal 5'-phosphate (Bound ligand (Het Group name = PLP) matches with 93.75% similarity)

• Enzyme class 3: E.C.5.1.1.18 - serine racemase.
• Reaction: L-serine = D-serine

L-serine (Bound ligand (Het Group name = MLI) matches with 75.00% similarity) = D-serine

• Cofactor: Pyridoxal 5'-phosphate

Pyridoxal 5'-phosphate (Bound ligand (Het Group name = PLP) matches with 93.75% similarity)

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

J Biol Chem 285:12873-12881 (2010)

PubMed id: 20106978

The structure of mammalian serine racemase: evidence for conformational changes upon inhibitor binding.

M.A.Smith, V.Mack, A.Ebneth, I.Moraes, B.Felicetti, M.Wood, D.Schonfeld, O.Mather, A.Cesura, J.Barker.

ABSTRACT

Serine racemase is responsible for the synthesis of D-serine, an endogenous co-agonist for N-methyl-D-aspartate receptor-type glutamate receptors (NMDARs). This pyridoxal 5'-phosphate-dependent enzyme is involved both in the reversible conversion of L- to D-serine and serine catabolism by alpha,beta-elimination of water, thereby regulating D-serine levels. Because D-serine affects NMDAR signaling throughout the brain, serine racemase is a promising target for the treatment of disorders related to NMDAR dysfunction. To provide a molecular basis for rational drug design the x-ray crystal structures of human and rat serine racemase were determined at 1.5- and 2.1-A resolution, respectively, and in the presence and absence of the orthosteric inhibitor malonate. The structures revealed a fold typical of beta-family pyridoxal 5'-phosphate enzymes, with both a large domain and a flexible small domain associated into a symmetric dimer, and indicated a ligand-induced rearrangement of the small domain that organizes the active site for specific turnover of the substrate.