PDBsum entry 4jm3

Unknown function

PDB id: 4jm3

Contents

Protein chains

258 a.a.

Ligands

EPE ×2

Waters ×555

PDB id:

4jm3

Name:

Unknown function

Title:

Enduracididine biosynthesis enzyme mppr with hepes buffer bound

Structure:

Putative uncharacterized protein mppr. Chain: a, b. Engineered: yes

Source:

Streptomyces hygroscopicus. Organism_taxid: 1912. Gene: mppr. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.85Å R-factor: 0.146 R-free: 0.176

Authors:

N.R.Silvaggi

Key ref:

A.M.Burroughs et al. (2013). Structural and functional characterization of MppR, an enduracididine biosynthetic enzyme from streptomyces hygroscopicus: functional diversity in the acetoacetate decarboxylase-like superfamily. Biochemistry, 52, 4492-4506. PubMed id: 23758195 DOI: 10.1021/bi400397k

Date:

13-Mar-13 Release date: 03-Jul-13

Protein chains

Q643B8  (Q643B8_STRHY) -  Enduracididine biosynthesis enzyme MppR from Streptomyces hygroscopicus

Seq: 302 a.a.

Struc: 258 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1021/bi400397k

Biochemistry 52:4492-4506 (2013)

PubMed id: 23758195

Structural and functional characterization of MppR, an enduracididine biosynthetic enzyme from streptomyces hygroscopicus: functional diversity in the acetoacetate decarboxylase-like superfamily.

A.M.Burroughs, R.W.Hoppe, N.C.Goebel, B.H.Sayyed, T.J.Voegtline, A.W.Schwabacher, T.M.Zabriskie, N.R.Silvaggi.

ABSTRACT

The nonproteinogenic amino acid enduracididine is a critical component of the mannopeptimycins, cyclic glycopeptide antibiotics with activity against drug-resistant pathogens, including methicillin-resistant Staphylococcus aureus. Enduracididine is produced in Streptomyces hygroscopicus by three enzymes, MppP, MppQ, and MppR. On the basis of primary sequence analysis, MppP and MppQ are pyridoxal 5'-phosphate-dependent aminotransferases; MppR shares a low, but significant, level of sequence identity with acetoacetate decarboxylase. The exact reactions catalyzed by each enzyme and the intermediates involved in the route to enduracididine are currently unknown. Herein, we present biochemical and structural characterization of MppR that demonstrates a catalytic activity for this enzyme and provides clues about its role in enduracididine biosynthesis. Bioinformatic analysis shows that MppR belongs to a previously uncharacterized family within the acetoacetate decarboxylase-like superfamily (ADCSF) and suggests that MppR-like enzymes may catalyze reactions diverging from the well-characterized, prototypical ADCSF decarboxylase activity. MppR shares a high degree of structural similarity with acetoacetate decarboxylase, though the respective quaternary structures differ markedly and structural differences in the active site explain the observed loss of decarboxylase activity. The crystal structure of MppR in the presence of a mixture of pyruvate and 4-imidazolecarboxaldehyde shows that MppR catalyzes the aldol condensation of these compounds and subsequent dehydration. Surprisingly, the structure of MppR in the presence of "4-hydroxy-2-ketoarginine" shows the correct 4R enantiomer of "2-ketoenduracididine" bound to the enzyme. These data, together with bioinformatic analysis of MppR homologues, identify a novel family within the acetoacetate decarboxylase-like superfamily with divergent active site structure and, consequently, biochemical function.