1J93

Crystal Structure and Substrate Binding Modeling of the Uroporphyrinogen-III Decarboxylase from Nicotiana tabacum: Implications for the Catalytic Mechanism

Summary for 1J93

• Entry DOI: 10.2210/pdb1j93/pdb
• Descriptor: UROPORPHYRINOGEN DECARBOXYLASE, SULFATE ION (3 entities in total)
• Functional Keywords: beta barrel, plastidial enzyme, crystallographic dimer, lyase
• Biological source: Nicotiana tabacum (common tobacco)
• Cellular location: Plastid, chloroplast: Q42967
• Total number of polymer chains: 1
• Total formula weight: 39667.57

Authors

Martins, B.M.,Grimm, B.,Mock, H.-P.,Huber, R.,Messerschmidt, A. (deposition date: 2001-05-23, release date: 2001-10-17, Last modification date: 2023-08-16)

Primary citation

Martins, B.M.,Grimm, B.,Mock, H.-P.,Huber, R.,Messerschmidt, A.
Crystal structure and substrate binding modeling of the uroporphyrinogen-III decarboxylase from Nicotiana tabacum. Implications for the catalytic mechanism
J.Biol.Chem., 276:44108-44116, 2001

PubMed Abstract: The enzymatic catalysis of many biological processes of life is supported by the presence of cofactors and prosthetic groups originating from the common tetrapyrrole precursor uroporphyrinogen-III. Uroporphyrinogen-III decarboxylase catalyzes its conversion into coproporphyrinogen-III, leading in plants to chlorophyll and heme biosynthesis. Here we report the first crystal structure of a plant (Nicotiana tabacum) uroporphyrinogen-III decarboxylase, together with the molecular modeling of substrate binding in tobacco and human enzymes. Its structural comparison with the homologous human protein reveals a similar catalytic cleft with six invariant polar residues, Arg(32), Arg(36), Asp(82), Ser(214) (Thr in Escherichia coli), Tyr(159), and His(329) (tobacco numbering). The functional relationships obtained from the structural and modeling analyses of both enzymes allowed the proposal for a refined catalytic mechanism. Asp(82) and Tyr(159) seem to be the catalytic functional groups, whereas the other residues may serve in substrate recognition and binding, with Arg(32) steering its insertion. The crystallographic dimer appears to represent the protein dimer under physiological conditions. The dimeric arrangement offers a plausible mechanism at least for the first two (out of four) decarboxylation steps.

PubMed: 11524417
DOI: 10.1074/jbc.M104759200

Experimental method

X-RAY DIFFRACTION (2.3 Å)