3GXO

Structure of the Mitomycin 7-O-methyltransferase MmcR with bound Mitomycin A

PDB DOI: https://doi.org/10.2210/pdb3GXO/pdb

Classification: TRANSFERASE
Organism(s): Streptomyces lavendulae
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2009-04-02 Released: 2010-04-21
Deposition Author(s): Singh, S., Chang, A., Bingman, C.A., Phillips Jr., G.N., Thorson, J.S.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.30 ?
R-Value Free: 0.255
R-Value Work: 0.202
R-Value Observed: 0.205

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.5 of the entry. See complete history.

Literature

Structural characterization of the mitomycin 7-O-methyltransferase.

Singh, S., Chang, A., Goff, R.D., Bingman, C.A., Gruschow, S., Sherman, D.H., Phillips, G.N., Thorson, J.S.

(2011) Proteins 79: 2181-2188

PubMed: 21538548 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1002/prot.23040
Primary Citation of Related Structures:
3GWZ, 3GXO

PubMed Abstract:
Mitomycins are quinone-containing antibiotics, widely used as antitumor drugs in chemotherapy. Mitomycin-7-O-methyltransferase (MmcR), a key tailoring enzyme involved in the biosynthesis of mitomycin in Streptomyces lavendulae, catalyzes the 7-O-methylation of both C9β- and C9α-configured 7-hydroxymitomycins. We have determined the crystal structures of the MmcR-S-adenosylhomocysteine (SAH) binary complex and MmcR-SAH-mitomycin A (MMA) ternary complex at resolutions of 1.9and 2.3 ?, respectively. The study revealed MmcR to adopt a common S-adenosyl-L-methionine-dependent O-methyltransferase fold and the presence of a structurally conserved active site general acid-base pair is consistent with a proton-assisted methyltransfer common to most methyltransferases. Given the importance of C7 alkylation to modulate mitomycin redox potential, this study may also present a template toward the future engineering of catalysts to generate uniquely bioactive mitomycins.

Organizational Affiliation

Division of Pharmaceutical Sciences, Wisconsin Center for Natural Product Research, School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.

Macromolecule Content

Total Structure Weight: 163.31 kDa
Atom Count: 10,864
Modelled Residue Count: 1,356
Deposited Residue Count: 1,476
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
MmcR	A, B [auth D], C, D [auth B]	369	Streptomyces lavendulae	Mutation(s): 0 Gene Names: mmcR EC: 2.1.1.316
UniProt
Find proteins for Q9X5T6 (Streptomyces lavendulae) Explore Q9X5T6 Go to UniProtKB: Q9X5T6
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q9X5T6
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
SAH Query on SAH Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain G [auth D] SDF format, chain K [auth C] SDF format, chain M [auth B] MOL2 format, chain E [auth A] MOL2 format, chain G [auth D] MOL2 format, chain K [auth C] MOL2 format, chain M [auth B] mmCIF format, chain E [auth A] mmCIF format, chain G [auth D] mmCIF format, chain K [auth C] mmCIF format, chain M [auth B]	E [auth A], G [auth D], K [auth C], M [auth B]	S-ADENOSYL-L-HOMOCYSTEINE C₁₄ H₂₀ N₆ O₅ S ZJUKTBDSGOFHSH-WFMPWKQPSA-N		Interactions Focus chain E [auth A] Focus chain G [auth D] Focus chain K [auth C] Focus chain M [auth B] Interactions & Density Focus chain E [auth A] Focus chain G [auth D] Focus chain K [auth C] Focus chain M [auth B]
MQA Query on MQA Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain H [auth D] SDF format, chain L [auth C] SDF format, chain N [auth B] MOL2 format, chain F [auth A] MOL2 format, chain H [auth D] MOL2 format, chain L [auth C] MOL2 format, chain N [auth B] mmCIF format, chain F [auth A] mmCIF format, chain H [auth D] mmCIF format, chain L [auth C] mmCIF format, chain N [auth B]	F [auth A], H [auth D], L [auth C], N [auth B]	[(1aS,8S,8aR,8bS)-6,8a-dimethoxy-5-methyl-4,7-dioxo-1,1a,2,4,7,8,8a,8b-octahydroazireno[2',3':3,4]pyrrolo[1,2-a]indol-8-yl]methyl carbamate C₁₆ H₁₉ N₃ O₆ HYFMSAFINFJTFH-NGSRAFSJSA-N		Interactions Focus chain F [auth A] Focus chain H [auth D] Focus chain L [auth C] Focus chain N [auth B] Interactions & Density Focus chain F [auth A] Focus chain H [auth D] Focus chain L [auth C] Focus chain N [auth B]
CA Query on CA Download Ideal Coordinates CCD File SDF format, chain I [auth D] SDF format, chain J [auth D] MOL2 format, chain I [auth D] MOL2 format, chain J [auth D] mmCIF format, chain I [auth D] mmCIF format, chain J [auth D]	I [auth D], J [auth D]	CALCIUM ION Ca BHPQYMZQTOCNFJ-UHFFFAOYSA-N		Interactions Focus chain I [auth D] Focus chain J [auth D] Interactions & Density Focus chain I [auth D] Focus chain J [auth D]

Modified Residues 1 Unique
ID	Chains	Type	Formula	2D Diagram	Parent
MSE Query on MSE	A, B [auth D], C, D [auth B]	L-PEPTIDE LINKING	C₅ H₁₁ N O₂ Se		MET

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.30 ?
R-Value Free: 0.255
R-Value Work: 0.202
R-Value Observed: 0.205
Space Group: P 2₁ 2₁ 2₁

Unit Cell:

Length ( ? )	Angle ( ? )
a = 87.841	α = 90
b = 98.844	β = 90
c = 171.045	γ = 90

Software Package:

Software Name	Purpose
DENZO	data reduction
SCALEPACK	data scaling
MOLREP	phasing
PHENIX	refinement
PDB_EXTRACT	data extraction
HKL-2000	data reduction
HKL-2000	data scaling

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2010-04-21

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2010-04-21
Type: Initial release
Version 1.1: 2011-07-13
Changes: Version format compliance
Version 1.2: 2017-11-01
Changes: Refinement description
Version 1.3: 2023-09-06
Changes: Data collection, Database references, Derived calculations, Refinement description
Version 1.4: 2023-11-22
Changes: Data collection
Version 1.5: 2024-11-20
Changes: Data collection, Structure summary